A REPORT TO THE
SURGEOM GENERAL

U.S. DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE

Public Health Service


KIDNEY
DISEASE

PROGRAM ANALYSIS

A REPORT TO THE
SURGEON GENERAL

      Prepared Under
    Direction of Office of
Program Planning and Evaluation
Office of the Surgeon General


FOREWORD

+The Public Health Service has a continuing responsibility to examine the
dr framework for effective decisioh-making required in the determination of
-health priorities and in the delineation of the most effective and
efficient methods of approaching the solution of the health problems that
  face us.  Therefore, in the spring of 1967 I convened a number of health
program analysis groups to study and analyze critically the subject and
program content in several specific areas of public health importance.
Each of these groups was to examine present and potential goals and
objectives, describe and discuss the current relevant state of knowledge
and current operating programs, and to develop and analyze to the best
of its ability alternative courses of action directed toward the achieve-
ment of these goals.

The analysis group responsible for this report on kidney disease was
under the direction of Benjamin T. Burton, Ph.D., Associate Director for
Program Analysis and Scientific Communication,, NIAMD, who was assisted
ably by staff from the various bureaus of the Publid Health Service.
Analyses of this kind are hampered by large data gaps which limit the
breadth and precision with which specific program alternatives and effec-
tiveness models can be developed.  These limitations, however, do not
invalidate the basic concepts contained or the alternative courses of
action considered.  In addition, the determination of the precise areas
of insufficient knowledge emphatically underscores our need for additional
research and development.  Thus, although program analyses in the health
field are still in the very early stages of development, it nevertheless
is important that we continue and improve upon previous efforts using
this analytic technique.

Dr. Burton, his staff, and members of the analysis group, are to be
commended for their efforts to comply with my request in such a short span
of time and for the quality of the report itself.  There can be no question
that this initial effort will be of value to me and my staff in considering
not only Public Health Service Programs directed towarh'kidney disease,
but also in the development of the methods and procedures.required for
subsequent analyses in the future.

&zli4@4/~
Surgeon General

iii


DEPARTMENT OF HEALTH, EDUCATION, AND WELFARE

               PUBLIC HEALTH SERVICE

IAL INSTITUTES OF HEALTH

BETHESDA. MD. 20014
ODE 301       TEL: 656X03                      ~uly 28, 1967

William H. Stewart, M.D.
Surgeon General
U. S. Public Health Service

Dear Dr. stewart:

In the spring of 1967, pursuant to your memoranda of February 27 and
March 15, you established a Kidney Disease Program Analysis Group      I/
and charged it with responsibility for an analytical study of kidney
disease in the light of present and future Public Health Service
goals and objectives.

This study, by a group of staff members from the various Bureaus of
the Service with competences relevant to the specific task, was
pursued actively until now.  This group was comprised of Dr. R. van Hoek
of the Bureau of Health Services, Dr. G. H. Escovitz of the Bureau of
Health Manpower, Mr. J. 0's. Francis, Dr. R. B. Freeman, and Dr. XV. A.
Hilmar of the Bureau of Disease Prevention and Environmental Control,
Mr. W. Anderson of your office, and Dr. W. R. DeCesare, Mr. E. Glaser,
Dr. W. H. Goldwater, Dr. D. E. Ksyhoe, Dr. K. N. Gershengorn and myself
of the National Institutes of Health.  Valuable quantitative analytic
competence was obtained through a contract with the Research Triangle
Institute,

The demands of this undertsking were high both in terms of,the magni-
tude and diversity of the disease area involved and in terms of the
very brief time available for the study. Nevertheless, I believe I
am expressing the consensus of the group when I say that the individual
members feel rewarded by the new knowledge and insights which`they have
gained during this study.

We have now completed our task and are pleased to present to you our
report.  Please be assured of our continued interest and desire to
cooperate.

           Chairman
Kidney Disease Program Analysis Group

V


PREFACE

_ This kidney disease program analysis, one of several similar

efforts being conducted at the present time, was originally conceived

as an.integral part of the planning and analytic effort required in

the implementation of the Planning, Programming, Budgeting System

throughout the United States Public Health Service.. It is being

published and distributed at this time with a two-fold purpose.  First,

to inform biomedical scientists and health professionals of some.of the

current thinking of the Public Health Service on approaches to combating

illness, disability, and death, due to kidney disease.   Secondly, to

elicit comment and criticism on the assumptions, methodologies, and

general character of the analysis in order to assist the Public Health

Service in efforts to improve upon this and subsequent studies related

to planning and evaluation of health programs.  It should be clearly

stated that in both regards it is recognized by members of the Public

Health Service and the analysis group itself that parts of the analysis

are totally dependent upon assumptions in areas in which there is very

rigorous scientific dispute, i.e., the etiology and subsequent patho-

genesis of certain kidney diseases, as well as assumptions regarding the

ease or practicability of .the delivery of preventive health services.

Nonetheless, the significance of these diseases in terms of human suffer-

ing and death challenges us to develop programs which will have the

maximum impact on human well being in relation to the resources that will

be available for these efforts.

vii


  The importance of planning and evaluation in any large scale

enterprise has gained increasing attention and emphasis during recent

years and has resulted in the establishment of a Planning, Programming,

Budgeting System through the Executive Branch of the Federal Government.

Although sometimes narrowly conceived as a limited management tool, its

broader effect of supporting more informed and therefore better decision-

making was clearly emphasized in the original memoranda transmitting the

Presidential decision to effect its wide-spread implementation.   The

approach emphasizes (1) clear articulation of goals and objectives, and
(2) alternative approaches to attaining these objectives.

  Numerous authorities on the Planning, Programming, Budgeting

System have emphasized the two major components of this -approach as
ltsystems analysis" and "program budgeting."  Systems analysis requires

a multidisciplinary approach by analytically oriented people skilled
c
in the use of quantitative techniques.  Program budgeting requires

thinking of the budget in terms of program objectives, i.e., purposes

realized rather than objects of expenditure, i.e., facilities, equipment,

and the like.  The unifying theme of program analysis is one of attempting

to relate program costs to program effectiveness.  That some problems

have been encountered in attempting to implement this budgetary system

is understandable.

  Charles J. Hitch, who directed the implementation of the Planning,

Programming, Budgeting System in the Department of Defense beginning in
1961, has repeatedly cautioned others on the need for adequate preparatory

work and development of the analytic competencies necessary to carry out

this activity.  It is noted by Mr. Hitch in the Nuffield Lecture delivered

last year,

Viii


"In Defense we had several hundred analysts at,the RAND

Corporation and elsewhere developing programming and

systems analysis techniques for a decade before the

Department attempted any large scale general application.

No remotely similar preparatory effort has gone into any

other governm'ental area and the number of trained and

skilled people is so limited that.they are inevitably

spread far thinner in other departments of government

than they were and are in Defense."

There has not been a comparable "preparatory effort" in the health

field devoted to the development of appropriate techniques and

methodology.  Moreover, more time is usually required than that avail-

able in the budgetary cycle to carry out cost effectiveness studies

that attempt to consider all costs, not just those that are readily

apparent and quantifiable.  Thus tremendous demands are placed on

individuals attempting to carry out suitable program analysis in the

health problem areas.  Nonetheless, it is important that a beginning be

made and that a body of experience be developed, critiqued, assessed,

and improved upon.

  In this analysis of kidney disease a priority was placed on

attempting to obtain a synergistic interrelation between analytically

oriented individuals with substantive knowledge of kidney disease and

qualified analysts.  The former were represented by selected staff

members of the Public Health Service serving on a task force.   The

quantitative analytic competency was obtained through'a contract with

the Research Triangle Institute.  Great credit is due to all individuals

iX


involved who tried to grapple with 'the objectives of kidney disease'

programs and alternative program approaches for meeting them.  It is

hoped that through their efforts, as well asthrough comment and

criticism that may be forthcoming from others, that we will be able

to improve sequentially the process and the product .in future analyses.

  The Office of Program Planning and Evaluation, Office of the

Surgeon General, is charged with the responsibility to define, develop,

and implement analytic techniques of this kind.  Any assistance,

criticism, or comments from professional groups, the academic communitY,

or interested individuals will be welcome and greatly appreciated.

X


Kidney Disease Program Analysis Group

Chairman:

Benjamin T. Burton, Ph.D.
Associate Director for Program Analys
and Scientific Communication
           and
Chief, Artificial Kidney Program
National Institute of Arthritis
and Metabolic Diseases
National Institutes of Health

Executive Secretary:  Kent N. Gershengorn, M.D.
                Staff Associate
             National Institute of Arthritis
                and Metabolic Diseases
             National Institutes of Health

William R. DeCesare, M.D.
Deputy Chief, General Clinical Research Centers Branch
Division of Research Facilities and Resources
National Institutes of Health

Gerald H. Escovitz, M.D.
Acting Assistant Chief
Continuing Education Branch
Division of Physician Manpower
Bureau of Health Manpower

Mr. John 0's. Francis
Chief, Program Studies Section
Kidney Disease Control Program
National Center for Chronic Disease Control
Bureau of Disease Prevention and Environmental Control

is

Richard B. Freeman, M.D.
Acting Chief, Preventive Programs Section
Kidney Disease Control Program
National Center for Chronic Disease Control
Bureau of Disease Prevention and Environmental Control


Mr. Ezra Glaser
Special Assistant to the Director for Scientific Communications
National Institutes of Health

William H. Goldwater, Ph.D.
Chief, Special Research Projects Branch
Extramural Programs
National Heart Institute
National Institutes of Health

Norman A. Hilmar, Ph.D.
Director, Office of Standards and Intelligence
Bureau of Disease Prevention and Environmental Control

Donald E. Rayhoe, M.D.
Chief, Transplantation Immunology Branch
National Institute of Allergy and

Infectious Diseases
National Institutes of Health

Robert van Hoek, M.D.
Chief, Office of Research
Division of Direct Health Services
Bureau of Health Services

Liaison:    Mr. William M. Anderson
        Program Analyst

Office of Program Planning and Evaluation
Office of the Surgeon General

Consultant:  Mr. Albert V. Alhadeff
        Operations Analyst

Operations Research and Economics Division
Research Triangle Institute

Consultant:  Mr. Jerome B. Hallan
       Operations Analyst

Operations Research and Economics Division
Research Triangle Institute

Consultant:  Dr. Edgar A. Parsons
          Director

Operations Research and Economics Division
Research Triangle Institute


TABLE OF CONTENTS

FOREWORD

LETTER OF TRANSMITTAL

PREFACE

CHAPTER 1 INTRODUCTION AND SUMMARY OF KIDNEY
        DISEASE PROGRAM ANALYSIS

I.   Introduction  ....................      1

II.  Summary   ......................      9

CHAPTER 2 KIDNEY DISEASE - CURRENT STATUS

I.   Introduction  ....................     38
II.  The Disease Problem   ................     38
III.  Diseases of Interest  ................     39
     References  .....................     63

CHAPTER 3 CURRENT KIDNEY DISEASE CONTROL PROGRAMS

I.  Introduction . . . . . . . . . . . . . . . . . . . .     64
II.  Specific Federal Kidney Disease Program Efforts . .     65
III.  Nonfederal Expenditures for Kidney Disease Programs.     82

CHAPTER 4 RESEARCH METHODOLOGY

I.  Introduction  .....................     85
II.   Diseases Studied  ..................     85
III.  Kidney Disease Programs Studied   ..........     87
IV.  Costs of Kidney Disease Program   ..........     89
V.  Benefits of Kidney Disease Programs   ........     90
VI.  Methodology Limitations   ..............     91
     Footnotes   .....................     93

CHAPTER 5 PROGRAM ANALYSIS

I.   Introduction  ..........  L  .........
II.  Infectious Diseases of the Urinary Tract  ......
III.  Hypersensitivity Diseases of the Kidney   ......
IV.  Kidney Diseases Related to Hypertensive
     Vascular Diseases   ................
V.  End-Stage Kidney Disease  ..............
    References and Footnotes  ........  ;  .....

94
97
121

139
168
185

xiii


CHAPTER 6 THE COST 0~ TREATING AIL PATIENTS    ,
      _ WITH CHRONIC KIDNEY FAILURE

I.  Introduction  ...................    196
II.  Approach to the Total Treatment
    of End-Stage Kidney Disease   .........  .,   196
III.  Calculation of Costs  ...............    201
IV.  Results   .....................    204
V.  Discussion  ....................    206
VI.  Feasible Approaches for End-Stage
    Kidney Disease Treatment  ............    208

xiv



Chapter 1

INTRODUCTION AND SUMMARY

OF THE

KIDNEY DISEASK PROGRAM ANALYSIS

I.  INTRODUCTION

A.  Objectives and Goals of the Report

  In the spring of 1967 the Surgeon General of the U. S. Public Health

Service established, among others, a health program analysis group to under-

take studies and analyses in the area of kidney disease.  Members of the

group were chosen from among senior staff of the National Institutes of

Health and other bureaus of the Public Health Service, who were responsible

for ongoing kidney disease-related programs or whose competence lay in the

areas of program planning and analysis.  In his charge to the group, the

Surgeon General directed it to describe and discuss the nation's kidney

disease problem, to outline the current state of knowledge and ongoing programs

in the area of kidney diseases, to consider advanced states of knowledge

and desirable programs, to develop goals and objectives for effective amelio-

ration of the problem, and to explore alternative approaches to the attainment

of these objectives.

An important part of the group's work was to be a logical analysis of

Programs leading to a solution or amelioration of the problem of kidney disease,


including:

1) A thorough discussion of goals and objectives and ways of measuring

  them;

2) A description of alternative approaches which could lead toward the

same objectives;

3) An analysis of the cost of reaching.various points on the continuum

of objectives by means of alternative approaches; and
4) A discussion of the basic assumptions upon which conclusions depend,

of uncertainties which affect the estimates used, and of the issues

which cannot be resolved at this time.

The work of the kidney disease program analysis group is intended to
guide the Office of the Surgeon General and, ultimately, the Office of the

Secretary, Health, Education, and Welfare, in the development of future progl
long range financial plans and budgets, and legislative proposals.

B.  Background

During the last five years, diseases of the kidney have steadily gained

in significance as an area of social importance for both Federal and non-

Federal research and service efforts.  Much of the impetus for this
increasing interest in kidney diseases has come from the development of
two dramatic but expensive therapeutic approaches to end-stage disease--
chronic hemodialysis and kidney transplantation.  The successes of both

techniques-- coupled with other research advances leading to a better under-
standing of kidney diseases --have led to a proliferation of activities.
directed toward reducing the morbidity and mortality these cause in the

Population.


There are a number of mechanisms, or program components, that are

traditionally brought to bear on a disease problem such as this.  These

are:

1) Expanded use of existing preventive techniques.

2) Expanded use of existing diagnostic techniques.

3) Expanded use of existing treatments, including chronic dialysis,

  kidney transplantation and conservative management (drugs, diets,

  etc.).

4) Laboratory and clinical research to produce new preventive,

  diagnostic, therapeutic and rehabilitative methods.

5) Increased specialized scientific medical and paramedical train-

  ing to provide the manpower needed for the research and treatment

  attack on the kidney disease problem.  This also includes

  continued postgraduate education to train practicing physicians

  in the use of the latest diagnostic and treatment modalities.

6) Increased public education to alert potential victims of kidney

  disease to seek medical help at the earliest possible emergence

  of warning signs.

7) Provision of specialized facilities not currently in existence

  which are essential for the execution of any of the above

programs.

  It must be understood from the outset that these program components

are interdependent in most cases.  For example, preventive techniques

exist that need further research to make them maximally effective for
braod application.  New treatment methods are useless if existing diag-

nostic techniques are not being applied in medical practice.  Because of


4

the present inadequacies of-existing treatments, be they dialysis,'trans-

plantation, or conservative management, a considerable research effort

is called for to increase their efficacy and economy to make them more

broadly useful.                                    :


C.  Considerationof Pto@%m Approaches

It is unlikely that a single program component would lead to a major

reduction in the national-kidney disease problem; therefore, a mixture

Of approaches will have to be employed by the Federal Government to
red&e the morbsdity and mortality due to kidney disease.  The total

funding level and the respective proportions for each approach in the
overall effort will determine, to a large extent, the benefits attain-
able in each successive year from this effort.  Advances in the state of

knowledge will affect the nature of this "mix" and will shift the'emphasis
from certain program components to others if we are to continue to derive

-. -

maximum benefits from the total expenditure of funds in this area.

Another important consideration in making choices for the funding of

specific program approaches is the effect of the expenditure of such
Federal funds on the overall national expenditure of funds in this area
including money spent by state and local governments, voluntary agencies,
universities and foundations, and the large segment of private expenditures
for medical diagnosis and treatment.  Here, the precise choice of direction
of the placement of Federal funds can determine to a large degree whether:
1) The resulting fruits of research or increased case findings at
    an early stage of the disease will stimulate an expanded use
   of nongovernmental money for earlier and more effective treatmen+--


5

with an overall beneficial effect on the state of kidney dise ct se

in the nation; or

2) Whether certain.choices for the expenditure of Federal funds

would serve to diminish the participation of the nongovernmental
                                                      /.

sector in efforts against kidney disease by mak&g it financially

more attractive to "let,Sam do it."

It is obvious therefore, that under a given set of conditions where

unlimited Federal funds are not available for the solution of a single

national disease problem, such as kidney disease, a rational balance must

be struck between the various relevant program approaches--investigative,

preventive, therapeutic and educational--so as to derive maximum benefits

from any current or possibly extended future Federal efforts.

D.  Program Analysis for Decision Making

  The future of Federal programs in the field of kidney diseases, be
                  . .

it for research, disease prevention, improvement of treatment methods
including hemodialysis and transplantation, or manpower training needs

decisions based upon a thorough, dispassionate and logical analysis.

With the aid of such analysis, public officials responsible for health

programs who face the problem of allocation of limited financial resources

.

in the struggle against kidney disease could make such decisions on the

basis of logical priorities.  These priorities would be based on the
present state of knowledge and on needs based on present morbidfties

and mortalities, as well as on the basis of anticipated developments

inthe future state of the art and the pertinent changes which they

are likely to introduce into the overall kidney disease picture.  The

fundamental intent of such an analysis and its raison d'etre is to.

provide maximum benefits in terms of prolongedi rewarding lives and reduced


morbidity for those afflicted with kidney,disorders and for those in

the population who will be stricken by it in the future, from the

aPPlicatioxi of Federal funds to research, disease prevention, treatment,

and manpower trainfng, directed against kidney disease.

E.  The Analysis

  Faced with the fact that its study and explorations could perforce

not be infinitely exhaustive it was decided that, for the sake of Practi-

cability and f&asibility, the heterogenous field of kidney disease be

divided into four 'tijor groups as follows:

    I.  Infetitious Diseases of the Urinary Tract,

   II.  Hypersensitivity Diseases of the Kidney,

  III.  Kidney Diseases Assodiated with Hypertension; and

   IV.  End-Stage Kidney Disease.

The first three groups encompass 'in toto about 75 percent of kidney
                                       --

morbidity and mortality; the fourth group, end-stage kidney disease,

exemplifies progressive and ultimately fatal kidney failure from all

possible causes.

   Each of these groups.accounts for a major percentage of overall kidney

morbidity and since each group of diseases was based on one-major distinct

causative principle it was felt that it is possible to discuss logically

each group individually in terms of the common overall mechanisms involved

and in tern= of the application of the vqrious possible program elements--

research, prevention, treatment, professional training and lay educatian--

to the solution of the problem which it represents.

   In addition to the first groups, there remains a miscellaneous group

of renal diseases of variable and distinct etiologies:


  a) Diseases of development (polycystic disease, hypoplastic

    kidneys, anomalies of position or structure, et&);

b) Renal involvement in metabolic diseases (diabetes, gout, amy-

    loidosis, oxaluria, etc.);

  c) Kidney damage due to obstruction (benign prostatic hypertrophy

    of the aged, kidney stones, etc.);

  d) Cancer of the kidney, both of primary or secondary origin; and

  e) Mechanical injury.

2.  Limitations

Programs and approaches for solution or amelioration of problems

associated with this latter mixed group of renal diseases are discussed

in the text of the report but were not subjected to individual cost-

effectiveness or benefit-cost analyses.  This decision was made to

avoid an unwieldy, and in many cases, impractical fragmentation of the


report.  Moreover, each one of these disorders may be the end result

of a primary disease for which there exist other, independent research

and preventive and/or curative efforts which, hopefully, would affect

beneficially the existing prevalence of the disease.

  For example, research advances of the last seven years in the area

of gout, once they are rigorously applied in the everyday practice of

medicine, will decrease considerably the prevalence of kidney damage due

to neglected or long standing chronic gout.  Similar considerations were

aPPIied to other disorders belonging to the residual mixed group of mis-

cellaneous diseases impinging on the functional integrity of the kidney.

  It was also decided to exclude neoplasms of the kidney from the

Program analysis.  Inclusion of this category in the present analysis


was felt to be undesirable because other extensiiie research tid public

                                                                 ',.

health progra&s affect the.srate bf the'art in cancer; moreover, in a
large percentage of patients afflicted with primary or s&conda`ry &ncer

of the kidney, kidney function per se doe&' not deteriorate until the
                                      -
extent of the lesion becomes overwhelming--at which point the life of
the patient is usually threatened by the neoplasm and its metastases

more than by the attendant renal failure.

The Present analy.sis was limited to kidney diseases which are pre-
                                                                           

dominantly chronic or to mecha&sms which though they may precipitate
*acute kidney disease, play a major role in eventual or potential chronicitP

of the disorder.  Tlius ) acute relial poisoning due to accidental causes

or suicide attempts, and nephrotoxic drug reactions were not included

in the analyses or program projections.

3.  Appendices

In the course of discussing possible programs and their specific

impacts, new ideas were develdped which seemed of sufficient interest

and potential benefit to be included in the report.  Subsequently, the

overall principles involved were fitted into tlie logical mainstream of

the report.  For the sake of brevity and continuity, however, the more

detailed projections or applications of such future programs were

included in appendices to the report, whenever they appeared of interest.

4.  Recommendations

  In projecting future programs and in analyzing their possible impact

on the mortality and morbidity due to each major sub-group of kidney

diseases, the committee attempted to avoid implied or overt recommendations.


It was felt that in each case 'the analysis and its logical extrapolations

spoke for themselves.

II.  SUMMARY

  The following summary presents the committee's most significant
generalized findings and a discussion thereof, and is not intended to

include all observations made.  These will be found in detail in the

body of the report.

   As a first step in its analysis in depth of kidney disease as a

national health problem, the committee studied each of the many diseases

of diverse etiologies which are encompassed in the general term 'kidney

disease'.  (Please see Chapter 2, Kidney Disease--Current Status)

In each case the current state of scientific knowledge for each disease

was determined including its underlying etiology, mechanisms of

pathogenesis, symptomatology, prognosis, severity and duration, methods

of d.iagnosis,  and treatment.  Where applicable, consideration was given

to existing gaps in knowledge, additional research needs, possible

prevention, diagnosis, and treatment under the conditions of present or

future states of the art, and interrelationships with other diseases.

Up-to-date statistical data were collected, such as prevalence in the

population, mortality, morbidity in terms of days of restricted activity,

average cost of treatment, and other relevant costs.

  Since the subject matter embraces a vast number of diseases with

highly divergent pathogenic mechanisms and nature, the committee made

decisions-in-principle concerning which of these would serve best as a


basis for a rational analysis under the limitations of the present study

(please see INTRODUCTION, E.,l., Organization of the Subiect Matter). The

three main groups of primary kidney diseases and end-stage kidney disease

common to them were utilized in the statistical analyses in this report.  This

group encompasses the overwhelming majority of kidney mortality and morbidity.

The remaining primary and secondary kidney diseases of statistically lesser

import were discussed in the text of the report but were not included in the

present program analysis.

  Subsequently a thorough study was made (Chapter 3, Current Kidney Disease

Control Programs) of the current governmental kidney disease programs and

relevant public and private expenditures for the nationwide treatment of kidnw

disease.  The latter includes cost of physician care, hospital care, nursing

home care, and other professional services for diagnosis and therapy of kidney

diseases, as well as the cost of drugs and net insurance costs.  In addition,

the cost was estimated for ongoing research efforts, for demonstration,

screening and detection programs, for education and training efforts and for

that portion of the cost of.construction of hospital and medical facilities

which can be prorated to the use of patients with kidney disease.

Program Analysis Models

   Based on the substantive information obtained and statistical and economic

data collected, the committee analysed the benefits to be gained by different

approaches to the solution or amelioration of the overall national kidney

disease problem at different expenditure levels of HRW funds. Models were

devised after experimentation with various statistical mechanisms and indices.


They are based'on a benefit+eost-analysis, for the four disease groups studied,

.
I.e., infectious diseases of the urinary tract, kidney diseases related to

hypersensitivity phenomena, kidney diseases related to hypertensive vascular

diseases, and end-stage kidney disease.  Four specific programs are considered

for each disease group.  These programs which are delineated by time, funding

level, and state of the art comprise the following:

    1) Hypothetical Program at the Current HEW Expenditure

       Level, Based on the Current State of the Art;

    2) Hypothetical Program at an Intermediate HEW Expenditure

       Level, Based on the Current State of the Art;

    3) Hypothetical Program at an Accelerated HEW Expenditure

      Level, Based on the Current State of the Art; and

    4) Hypothetical Program for Fiscal Year 1975, at-an Accelerated

HEW Expenditure Level, Based on the Expected Advanced State

of the Art in 1975.

  Each program consisted of a hypothetical situation where a specific level

of HEW program funding was divided.among a rational mix of program components
(screening, diagnosis and treatment, research, training, etc.) based on the

particular characteristics of the specific disease group involved, and was

applied to specifically involved or particularly vulnerable groups or, as the

case may be, to the eniire population.  vj.r&=. tien&fzit's I.;&&*~e 'f+& -kg&*
pk$$&& tire .,:;&&;;g&&t& `.,*d '1&&t&, .fk :&i ,$&'z&&~&;,,l*&*,~on ory

mopp+gy; $j-??g~&e, I ',- :`.&na' 'm&jf,j;i~ &&,"&;~&;ey &&t&&j- Wherever the mking

of assumptions was unavoidable, the resulting estimates were based on the best

scientific evidence and available data and were held within conservative limits.


Benefit indic'eS were quantified in terms of.the reduction in annualpr"

mortality* .the reduction in annual morbidity (number of sick days per year)
and in .terms of ,the disease prev,alence,in the total population dueto tu4

spf&fic type of kidney disorder analyzed* "%hich would accrue thanks to the

impact of the various program components--such as research advances, disease

prevention and improved treatment.  It was felt that these specific benefit
indices were more appropriate for the purposes of this study than other
potential indices such as "loss of productivity," loss of gross national
product due to the death.of individuals, or loss to the Federal Government of

tax revenue due to death or inactivity of individuals.  Moreover, it was felt

that- it would be more desirable to quantify the benefits which could accrue
from HEN-supported programs aimed at the kidney disease problem in terms
related directly to the human beings who are to benefit from such expenditure,
rather than in terms of a highly impersonal inert commodity--dollars.  The fact

that mortality and morbidity figures could be manipulated statistically just
as well as dollars, but could be used without introducing too many estimates
and assumptions ("What is the price of a human life?", "How much money is lost,
and to whom, when a sick person does not report to work?") induced the committee
to choose these indices for its benefit-cost analyses.

A detailed explanation of the various postulated programs and the analysis
of their potential benefits will be found in Chapter 4, Research Methodology,

and Chapter 5, Program Analysis.  The nature of these programs, and the benefits
and costs associated with each of the four programs in each disease group are

summarized and discussed below.


I.3

Summary of Alternative Programs for Individual Disease Groups


1.  Infectious Diseases of the Urinary Tract

  a. Hypothetical Program at Current HEN
    Expenditure Level, Based on the Current State of the Art

    A major component of this program is the screening of the

following specific high-risk groups: patients in hospitals and

nursing homes, non-hospitalized pregnant females, and non-

hospitalized diabetic patients.  This would be followed by the

establishment of definitive diagnoses and vigorous treatment .of

any kidney infections discovered.  A second major projected

program component is laboratory and clinical research directly

relevant to infections of the kidney.  bther program components

are concerned with the education of medical personnel and the

specific training of additional manpower.  The cost to HEW is

estimated at $9,203,000.

Short-term benefits of this program (discernible when the

program reaches full operation), would be represented by an annual

reduction in mortality of 70, a reduction in prevalence of

3,231,260 cases and a reduction of 15,962,420 morbid days in the

involved vulnerable group.  Long-term benefits (to be seen many

years after the program becomes fully operational) are represented

by the avoidance of irreversible, fatal uremia in 1,750 individuals

per year.

b. Hypothetical Program at an Intermediate HEN Expenditure Level,
  Based on the Current State of the Art

At the intermediate program level, HEW expenditures are about

two times greater than in the preceding program.  Again a major

component of this program is the screening, diagnosis and treatment




of urinary tract infections.  An additional high-risk group has

been added:  females 6 to. 9 years of age. The.cost .t.o HEW is

estimated at- $20,179,000.
           

  Short-term benefits attributable to this program are quantita-

tively greater (percentage reductions do not change), due to the

addition of another high-risk group;  .A reduction in short-term

mortality of 70 is again expected due to the very low mortality

from infections of the urinary tract in the added vulnerable group.
Prevalence is reduced by 3,243,860 and morbid daysby 16,273,640.

A yearly reduction of fatal end-stage kidney disease by 1,770 is

expected.

Expansion of the proposed basic program (see previous model)

to a level which is two times larger, in an effort to include an

additional vulnerable group, did not result in a near-proportionate

increase in benefits.. Once a new potentially vulnerable group

was included in which the percentage of individuals harboring

urinary tract 'infections was much lower than in the previous hypo-

thetical situation, the point of rapidly diminishing returns was

reached.  Thus an indication was received of the possible limits

of effectiveness for a screening-diagnosis-treatment program for

infectious diseases of the kidney in the general, non-morbid

population under conditions of the current state of knowledge.

C.

Hypothetical Program at an Accelerated HEW Expenditure Level,
Based on the Current State of the Art

In this projected situation, the HBW expenditure level is about

two and one-half times greater than the current level.  Again, a

major component of this program is the screening, diagnosis and


treatment of infections of the urinary tract.  The high-risk group

at which the program is aimed has been expanded to include all
females under 21 years of age.

The short-term benefits attributable to this program include

a similar percentage reduction in mortality and morbid days as
before, but since a larger vulnerable population was involved,

quantitative benefits are greater.  The cost to HEW is $27,394,000.

  Short-term benefits include an annual reduction of 70 deaths,

3,292,860 cases, and 17,483,880 morbid days.
Long-term benefits are represented by the elimination of
irreversible, fatal uremia in 1,870 individuals per year.
  The same conrnents made on the less-than proportionate increase
in benefits in the intermediate program apply, even more strongly,

'to this hypothetical situation.  It is obvious that under the

conditions of the present state of the art the limits of effective-
ness for this approach have been reached at the previous level

of expenditure, in the intermediate program.

d.  Hypothetical Program, for Fiscal Year 1975 at an Accelerated
HEW Expenditure Level, Based on an Advanced State of the Art

In this projected situation, the HEW expenditure is about

three and one-half times greater than the original program.  Funds

for research have been increased considerably.  Screening, diagnosis

and treatment still remain a major program component.

Under an advanced state of the art it is assumed that the

extensive research efforts have made possible:
1) More effective antimicrobial therapy,

2) Better understanding of the pathophysiology of urinary
   tract infections, and


3) Better understanding of the natural history of

pyelonephritis.

The cost to HEW is estimated at $31,228,000.

Short-term benefits now include an annual reduction of 80

deaths, 5,630,780 cases, and 26,064,430 morbid'days. Long-term

benefits are represented by. the elimination of irreversible,

fatal uremia in 4,125 individuals per year.

2.  Hypersensitivity Diseases of the Kidney

a. Hypothetical Program at the Current HEW Expenditure Level,
  Based on the Current State of the Art

It was concluded that present knowledge of hhersensitivity

diseases of the kidney is insufficient to justify a special program

of case finding, diagnosis and treatment since it is doubtful

whether it could make an effective impact on current morbidity

and mortality figures due to these diseases.  The most important

projected program component is laboratory and clinical research

relevant to immunology and hypersensitivity diseases of the kidney.

An additional component is postgraduate physician education,
research training, and expansion of research facilities. The

cost to HEW is estimated at $7,480,000.
Short-term benefits expected are a reduction of 610 in
immediate mortality, primarily due to the postgraduate physician
                                    . .

education and.consequent improved medical practice.  No immediate
benefits are expected from the research effort undertaken.
A 1% reduction in mortality, a 5& reduction In prevalence

and a 65% reduction in morbid days is anticipated over a future


ten-year period as a result of this program primarily due to

anticipated research advances, and secondarily due to a higher

quality of medical care (see anticipated benefits for 1975).

This was one of the most uncertain estimates.made.; it was based

on the research advances of the last 10 years and on the arbitrary

assumption that the rate of new developments will remain the

same.

b.  Hvpothetical Program at an Intermediate HEW Expenditure Level,
   Based on the Current State of the Art

  In this situation, the program components have not changed

essentially, but the HEW expenditure level has been increased.

The most important program component is, again, research. The

cost to HEW is estimated at $20,000,000.

Short-term benefits would remain similar to those described

at the previous, lower expenditure level (see above).

  Long-term benefits will only be increased significantly over

the previous program if the funds for research in the latter had
been a &aiting factor for productive research.

c. Hvpothetical Program at an Accelerated HEW Expenditure Level,
  Based on the Current State of the Art

In this situation, the program components have not changed

essentially, but the original HEW expenditure level has been

tripled.  The most important program component is, again, research.

The cost to HEW is estimated at $23,875,000.

Short-term benefits would remain similar to those described

at a non-accelerated HEW level (see above).


Here again; long-term benefits will only be increased
                               
significantly over the previous program if the funds for.
research in the latter had been a limiting factor for productive

research.

d. Hypothetical Program at an Accelerated HEW Expenditure Level,
Based on an Advanced State of the Art .(1975)

  Under an advanced state of.the art, it is assumed that the

preceding research has resuited in the development of effective
means of preventing hypersensitivity diseases of the kidney, or

of treating them.  Possible examples are:

1) An effective anti-streptococcal vaccine;

2) Failing that, discovery of a means for early detection of
streptococcal infections and for the interruption of the
                                      -- .

immunological mechanisms that lead to acute glomerulonephritis

and/or

3) Increased understanding of the meaning of proteinuria and
means for identification and treatment of individuals in

whom it heralds eventual chronic renal disease.

A program based on-the use of an anti-streptococcal vaccine in
a majority of the population and on early detection and treatment

of persistent proteinuria would yield the following short-term

benefits:  an annual reduction in mortality of 770, a reduction in

prevalence by 62,250 cases and a reduction of 2,610,OOO morbid days

in those affected.

Long-term benefits would be represented by a decrease of 8,610

individuals per year who would otherwise reach end-stage kidney

failure in the future.  The cost to HEW has been estimated at

$77,320,000.


   It is important to note that any of the program approaches

involving the advances mentioned above would have a profound

impact on the prevention and treatment of hypersensitivity diseases

in general, such as rheumatic fever, rheumatic heart disease,

and others.

8.  Kidney Diseases Associated with Hypertension

  a. Hypothetical Program at the Current HEW Expenditure Level,
    Based on the Current State of the Art

   The projected program consists of three major components:
   1) Screening, diagnosis and treatment of individuals 17
     years of age and over with curable (non-essential)
     hypertension and non-curable hypertension;
   2) Postgraduate education of practicing physicians and
     education of the population relevant to early recognition

      and treatment of the disease; and

    3) Laboratory and clinical research.
B relatively minor component for research training of physicians

  and allied personnel is. also included.  HEW costs are estimated at

  $9,180,000.

  Estimated annual short-term benefits include a decrease in
mortality by 7,830, a reduction in prevalence of 54,000 cases, and
a reduction of 5,959,OOO in morbid days due to hypertensive disease.
It has been assumed that approximately 30X of the benefited
individuals with hypertension have renal involvement. Thusthe
figures for benefits accruing to patients with renal disease
associated with hypertension are 2,190, 27,000; and 1,802,000,

respectively.


20

A reduction of 4,330 per year in the number of individuals

dying from irreversible uremia is expected as a long-term benefit.

b.  Hypothetical Program at an Intermediate HEW Expenditure Level,
  Based on the Current State of the Art

The projected program is similar to the preceding one except

that under an increased funding level (about two and one-half

times greater than before) an additional population group is

subjected to screening, diagnosis and treatment. Reference is to

persons 17 years of age and over who have had no care from a

physician during the preceding .year. The program affecting the

additional group is expected to cover a six-year cycle.  Estimated

costs for HEW are $21,207,000.

Estimated annual short-term benefits for patients with renal

involvement are now increased to 2,270 avoided deaths, a reduction

in prevalence of 34,880 cases and a reduction in morbid days of

2,056,820.  Expected long-term benefits are estimated to include

an annual reduction In fatal end-stage uremia of 4,820 cases.

c. Hypothetical Program at an Accelerated REW Expenditure Level,
  Based on the Current State of the Art

This program is similar to the one postulated for an inter-
mediate level of expenditure exkept that the program affecting the
additional high-risk group of previously unscreened individuals
has been accslerated to cover a three-year cycle rather than six

years.  The estimated cost to HEW is $28,639,000 (about three

times the original level of expenditure).
Estimated annual short-term benefits for patients with renal
involvement now include 2,380 avoided deaths, a reduction in
prevalence of 42,750 cases, and a reduction in morbid days of


2,311,340.  Expected long-term benefits are estimated at an

annual reduction in end-stage uremia of 4,820 cases.

  In this case, further expansion of the program above the

intermediate level did not appear warranted by the resulting increase

in benefits, which was very far from proportional. Here again,

an indication was received of the possible limits of effective-

ness for a screening-diagnosis-treatment program for kidney

diseases associated with hypertension in the non-symptomatic

population ("individuals who have not seen a physician during

the preceding year"), under conditions of the current state of

knowledge.

d.  Hypothetical Program at an Accelerated HEW Expenditure Level,
  Based on an Advanced State of the Art (1975)

  Under an advanced state of the art it is assumed that the

preceding extensive research efforts have resulted in the following:
1) Advances in understanding of the underlying cause(s) of

    hypertension;

2) Improved diagnostic tests for detecting hypertension;
3) Specific effective therapy(ies) directed toward the various

  underlying causes; and,

4) Advances in surgical methodology for the types of hypertension

   amenable to such treatment.

Screening, diagnosis and treatment still remain the major program

components in this projected situation.  The target population is
the same as in the preceding programs.  HEW costs are estimated at

$35,832,000.

Estimated annual short-term benefits for patients with renal

involvement include a 9,300 decrease in mortality, a reduction of


289,700 in prevalence and a reduction in morbid days of 5,579,OOO.

    Long-term benefits are expected to result in an estimated

  annual avoidance of fatal end-stage kidney disease in 9,480

   individuals.

4.  End-Stage Kidney Disease

  End-stage kidney disease as indicated earlier exemplifies

progressive and ultimately fatal kidney failure from all causes.
Because of the unique and costly treatment methods currently.available

this group was studied not only from the standpoint of the four program

alternatives (used for the three primary disease groups) but also from
the standpoint of a program which attempts to treat all patients with

chronic kidney failure.

a.  Hypothetical Program at Current HJZW Expenditure Level Based
  on the Current State of the Art

The major component in this program consists of treatment of

patients in end-stage renal failure by dialysis and/or kidney

transplantation.  A second program component is laboratory and

clinical research relevant to both treatment modalities, develop-

mental research for dialysis hardware improvement, and development

of organ preservation technology and facilities.  A third program

component, considerably smaller, involves training of relevant

manpower and provision of needed facilities.  The estimated HEW

cost is $21,000,000.

  The benefits in this program are measured in terms of mortality

avoided in the total group of patients in irreversible renal failure

whose lives are in jeopardy.  Under the circumstances of this

particular program, 600 patients will be maintained through


chronic dialysis and 90 lives yearly will be saved through

successful transplantation.

  This program of dialysis and transplantation, at current

HEW expenditure levels, provides life-saving care for about 1.5% of

the number of patients threatened by death during that particular

year because of end-stage kidney disease.

b.  Hypothetical Program at an Intermediate HEW Expenditure
  Level, Based on the Current State of the Art

  In this projected situation the level of HEW funding has

been increased appreciably to reflect the immediate urgency posed

by the threatened lives of patients in irreversible renal failure.

Treatment expenditures have been increased by a factor of 5 over

the previous level, research expenditures by a.factor of 1.5 and

training and facilities by a factor of 5.

  Under the circumstances of this particular program, about

1,150 patients would be maintained by chronic dialysis and about

420 individuals would be cured by transplantation.

This program which involves about $56,000,000 of HEW funds

will provide life sustaining treatment for about 3% of the annual

number of persons who have end-stage kidney disease during the

first year of the program.  During the second year of such a

program, however, because of the carry-over of about 80% of the

patients dialyzed during the preceding year,:the same sum of

money will provide treatment for considerably less than 3% of the

uremic patients threatened by death during the second year.
Because of the increasing carryover load of dialysis patients


from previous years, this limiting effect will increase with

each successive year of such a program.  Unless the budget,


  manpower, and facilities are increased considerably during each

succeeding year over the respective previous levels, only a

small proportion of

to end-stage kidney

in such a program.

the total group threatened with death due

disease each year will actually be saved

This problem is discussed.in greater detail

later in this summary chapter and particularly in Chapter 6,

The Cost of Treating All Patients with Chronic Kidney Failure.

c. Hvpothetical Program at an Accelerated HKW Expenditure
  Level, Based on the Current State of the Art

  In this projected situation, the level of HEW funding has

been increased tenfold to reflect the inunediate urgency posed

by the threatened lives of patients in irreversible renal

failure.  Although the overall funding is increased tenfold in

an effort to extend treatment to as many patients as possible,

research funds have only been doubled over the current level,

since this was felt to be the limit of research and development

which could possibly be productive at this point in time.

Training and facility expenditures have also increased tenfold

because of the immensely increased patient load.
Under the circumstances of this particular hypothetic program
4,100 lives will be maintained through chronic dialysis and
3,575 lives will -be saved.yearli through successful xransplantatiou.

This program, which utilizes $210,000,000 of HKW money (about

$170,000,000 of which are expended for patient care), provides


.treatment for about 15% of the overall number of patients

threatened by death because of end-stage kidney disease and

available during the first year of the program.  The same

problem of buildup of carry-over patients in future years exists

under this program and interferes with the achievement of its

goals unless the level of expenditure is raised appreciably

during each succeeding year.

d.  Hvpothetical Program at an Accelerated HEW Expenditure
  Level, Based on an Advanced State of the Art in 1975

Under an advanced state of the art, it is assumed that the

preceding extensive research efforts have resulted in the

following advinces:

1) Dialysis treatment can be carried out by the patient

essentially independently of treatment facilities

(except for periodic medical'checkups), and the debili-

tating complications seen in patients on dialysis

therapy have been eliminated;

  2) A highly developed program for organ matching and

    preservation is in existence, &nmunosuppressive techniques

    are highly effective, transplantation survival is vastly

    increased, and the procedure can now be carried out in

    most of the general hospitals in the United States; and

  3)  In the case of both treatment modalities the cost has

    been reduced appreciably.

In this projected situation, the total HJN expenditure is

smaller than the accelerated budget level assuming current state

of the art (see above).  The expenditures for research have been



decreased considerably because of the research and development

achievements of previous years.  Training and facility expendi-

tures have remained on the same accelerated level because of

the large patient population which is being treated.  The major

program element is treatment of all suitable patients by

transplantation,  since this is a one-time treatment.   This

permanent treatment is, of course, preceded by supportive

dialysis and patients in whom the procedure is unsuccessful

are also maintained by dialysis pending a second attempt at

transplantation.  About 12,000 of the remaining patients in

renal failure who are not suitable surgery candidates are placed

on life-long dialysis.

Under the circumstances of this highly idealized program,

about 16,000 lives will be saved annually through transplantation

in the vulnerable group.  In addition, about 11,400 individuals

                                                       .

will be maintained through chronic dialysis; most of these will

be carry-over patients from previous years.

This hypothetical program which utilizes $150,000,000 of

HEW funds, most of which are devoted to patient treatment, provides

treatment for about 55% of the number of patients threatened by

death because of end-stage kidney disease during the first year

of its operation (1975).  It is important to note that advanced

age and concurrent disorders prevent the successful application

of transplantation and/or chronic dialysis to every one of the

approximately 50,000 patients who present themselves each year

with end-stage kidney disease.


27

  A comparison summary of the results of the three hypothetical
situations with regard to end-stage kidney disease shows that

an immediate tenfold increase of HEW expenditures primarily

for patient treatment under conditions of the present state of

the art would, at best, approach a solution for 15% of the patient

population threatened by fatal kidney failure in the first year;

thereafter, a progressingly smaller percentage of the vulnerable
group could be helped.  (This situation is, of course, wholly

hypothetical, since  there does not exist sufficient medical man-

power either qualified or willing to participate in such a program).

Advances in the state of the .art which can be expected through a

judicious doubling of HEW support for research and passage of
sufficient time to permit the unfolding of research achievements
would make it possible to save the lives of about 55% of the

threatened patient population in the first year of such a program
with a smaller expenditure of funds for patient care than was
postulated for the previously described accelerated level program

under the current state of the art, which only starts to take

care of 15% of those in need of treatment.

e.  Hypothetical Program Attempting Treatment of All Patients
  with Chronic Kidney Failure

1) Introduction

Whenever consideration is given to the problem of

ultimately fatal chronic renal failure, the question

is frequently raised of what it would cost to make
an attempt at treating all patients threatened by a


28

uremic death-- either with the aid of lifelong chronic

dialysis or through attempts at kidney transplantation

whenever donor kidneys may be available.  This

question is usually raised by well-meaning individuals

for humanitarian reasons.

Approximately three-fourths of the 50,000 patients who

present themselves each year with fatal end-stage kidney

disease are known to be above the age of 60. This fact
&get&r with the many concurrent other disorders

afflicting most of these patients (and the rather stringent

requirement for emotional suitability for chronic dialysis)

make it extremely unlikely that a large-scale application

of either transplantation or chronic dialysis to all

or practically all of these 50,000 individuals would be

successful.  A further discussion of practical restraints

in terms of requirements for specialized manpower and

facilities is found in Chapter 6 (The Cost of Treating

All Patients with Chronic Kidney Failure), Section V.

Nevertheless, although the original mission of the Kidney
Disease Analysis Group did not include the preparation
of an answer to this question concerning the cost of a

hypothetical "total push" program, it was felt that an

analysis of this cost would be a natural corollary to
the preceding analyses of costs and benefits of optimal

Programs aimed at the major primary kidney diseases and

at end-stage kidney disease.  In any consideration of


29

possible programs for the amelioration of the kidney

disease problem, an attempt to treat all patients threatened

with a uremic death regardless of the possible,costs,

for humanitarian reasons, represents one extreme in a

broad spectrum of possible programs. The committee

therefore felt that this hypothetical cost should be

ascertained to serve as a maximal bench mark for any

intensive attempt at program analysis or planning.

The details of such a hypothetical total push program

and the necessary calculations are found in Chapter 6.

2) Calculation of Costs

It was obvious that the mere calculation of the cost

of the first year of such a total push program would

leave a misleading impression as to the true long-term

expense involved if such an approach is chosen.   Because

of the significant rate of survival from year to year

among the patients treated by chronic dialysis, the cost

of extending treatment to all those needing it in sub-

sequent years will increase considerably with the passage

of time.  It was therefore decided to calculate the

actual cost of the treatment of all individuals requiring

it (the new group of vulnerable uremic patients presenting

itself each year, the patients on lifelong dialysis who

are survivors from previous years, and the patients in

whom transplantation was unsuccessful and who must be

maintained with the aid of chronic dialysis) for as many


years as needed after the start of the program until

a year was reached which could be considered

characteristic of a "steady state."  At this particular

point in time the number of new patients included each

year in this program would equal the number of patients

dying in the same year,  and in this situation a constant

or near-constant yearly cost of the program would be


reached.

Calculations showed that under the conditions of this

program its yearly cost would increase greatly each

year during the first 15 years, that the subsequent

yearly increases in cost would be of a somewhat lesser

magnitude but still highly significant, and that an

asymptotic curve approach would show that the steady

state would not yet be reached by the twenty-fifth year.

Obviously one can expect research advances to occur

well within the first 10 or 15 years which would modify

greatly the respective efficacies of transplantation

and hemodialysis and their costs.   It was therefore

decided that it would be unrealistic to report the cost

of the hypothetical total push treatment program for

end-stage kidney disease in terms of the eventual yearly

cost of the steady state after 25 years.  Rather, it was

felt that it would be sufficiently indicative of the true

costs to be expected to report the cost of the first year

of such a program (the lowest yearly cost), the cost of


the fifth year (a realistically foreseeable sum which

is not likely to be influenced significantly by changes

in the state of the art), and the cost of the

fifteenth year (which is considerably higher than the

cost of the fifth year and begins to approach the

markedly higher eventual cost of the steady state year).

  To obtain a realistic range of cost, the calculations

  were done on the basis of two cost assumptions for each

  treatment modality:  A higher "present cost" figure

  which reflects accurately today's costs of transplantation

  and chronic dialysis, and a realistically reduced "future

  cost" figure for these treatment modalities.

3) Results Obtained


   First Year

Based on "present cost" figures, the cost of attempting

to treat 40,000 patients out of the total vulnerable

population of 50,000-during the first year of this

hypothetical program, by means of chronic dialysis or

kidney transplantation, would be $611,000,000.

(Note:  If an attempt is made to treat all 50,000 vulner-

able patients, the cost of this program during the first

year will be $761,000,000.)

If the calculation for the first year is based on the

less likely "future cost" rate, the respective figures


would be $422,000,000 and $522,000,000.

Fifth Year

The cost of this program in the fifth year of its

existence will range between $1,043,600,000 (based on

the low, "future cost" figure) and $1,543,415,000

(based on the higher, "present cost" figure). In

this year, 102,161 patients would be treated under the

program by transplantation or chronic dialysis.

Fifteenth Year

The cost of this program in the 15th year of its existence

will range between $1,816,000,000 (based on the low

"future cost" figure) and $2,702,000,000 (based on the

higher "present cost" figure).  In this year, 179,401

patients would be treated under this program, by trans-

plantation or chronic dialysis.

In view of the fact that it is anticipated that research

advances evolving during and after the first fifteen

years of the program would introduce considerable improve-

ments into both treatment modalities and would influence

true costs significantly, projected expenses for the

twentieth and twenty-fifth year of the program were calcu-

lated but not reported.  It should be noted, however,

that the population which would require treatment during

each year of this program would continue to grow and thus

the yearly costs would increase, until a point beyond the

twenty-fifth year at which a steady state would be reached.


33

B.  A Total Program Aimed at Kidney Disease


   1.   Introduction

    It is evident from the foregoing models that concentration in

future programs merely on the treatment of end-stage kidney disease

is not likely to solve the problem of annual deaths due to irreversible

uremia unless unlimited funds are available for an indefinite continua-

tion of such a program.  Thus, steps must be taken to decrease the

number of people who enter the irreversible fatal stage each year by

a systematic prevention or treatment of the primary kidney diseases

which initiate their progressive downhill course.   It is obvious

from the analyses in the three major kidney disease groups---infectious,

hypersensitive and hypertensive--that the otherwise inevitable annual

reservoir of patients with irreversible kidney failure can be

diminished considerably through vigorous programs activated to deal

with each of these groups.  The application of relatively minor :funds

in the group of infectious kidney diseases to stimulate systematic

screening of high-risk groups followed by diagnosis and treatment,

even within the current state of the art and without awaiting addi-

tional advances due to ongoing or future research, can bring about a

significant future reduction in the number of end-stage patients,

Continued and expanded research activities will be necessary to

increase the percentage of patients ultimately benefitted by this

approach.

  In the area of hypersensitivity diseases involving the kidney

there appears to be no promising mode of attack in sight except for

the launching of a systematic research effort intended to increase


our knowledge of the disease mechanisms involved.  Here,  the sooner

this effort is started the greater the likelihood of a reduction of

the number of end-stage victims in the near future.  The promise for

benefits to be derived from this type of research effort is such

that it should not be postponed--particularly since any new effective

treatment or prevention modality would produce major benefits in the

entire field of hypersensitivity diseases, such as rheumatic heart

disease,  rheumatoid arthritis and others.

  In the group of hypertensive diseases of the kidney an immediate

start, within the current state of the art, of screening, diagnosis

and treatment can begin to diminish the number of patients who will

eventually require end-stage treatment because of their progressive

renal involvement.  Simultaneous research efforts are likely to make

this particular portion of the overall program more effective as time

goes by, in the same fashion in which the new antihypertensive drugs

developed during the last ten years have succeeded in decreasing by

about 50 percent the mortality due to malignant hypertension.

  Thus, a meaningful Federal program to reduce the annual mortality

due to kidney disease and aimed at a general reduction of the prevalence

of the various kidney diseases must perforce be a multifactorial one

which brings into play all of the program components--research,

prevention,  treatment and education--available in our armamentarium.

An optimally proportioned mix of these program components must be

present to yield maximum benefits in overall number of lives saved.

This last concept includes not only deaths avoided today but deaths to

be prevented in the years to come. Needless to say, such a total


program, to be meaningful and productive, must be aimed at all three


35

major primary kidney diseases, as well as at end-stage kidney failure.

2.  Structure of Total Program Models

  In order to arrive at the overall makeup of such a mixed attack on

the problem of kidney disease, Tables I and II were prepared.   These

Tables outline the composition of four hypothetical overall programs--

three at different levels of expenditure and under the conditions of

the present state of the art,  and the fourth under the conditions of

the expected advanced state of the art in 1975.  Table III presents

the benefits estimated for the four overall programs.  Scanning thi:s

table horizontally provides an intercomparison of benefits in the

four disease categories.  A vertical scan of this table provides an

indication of the sensitivity of the four kidney disease categories

to changes in expenditure levels.

  These projected total programs consist of a combination of the

individual models of programs aimed at the various major primary kidney

diseases and end-stage kidney failure which have been mentioned pre-

viously and which are described in detail in Chapter 5.  Thus, each

hypothetical total program divides a specific level of HEW funding

among a rational mix of program components the composition of which,

in turn, is based on the conclusions from the previous analyses.

  Figures 1 and 2 provide another illustration of the qualitative

and quantitative makeup of the first three total programs postulated

for the current state of the art in Tables I and II.  These pie charts

serve to illustrate very graphically the influence of the available

level of funding on the relative composition of these hypothetical


programs.  Thus, under circumstances of small budgets the percentage

of treatment funds tends to be small, and that of research tends to


Table I

HE!4 COST SUMMARY
  (Sl,OGO)

Prevention (including education h administration)
Diagnosis and Treatment

                 Sub-Total

Intermediate     Expenditure Level*
Diagnosis, Prevention, Treatment
Prevention (including education & administration)
Diagnosis and Treatment

                  Sub-Total

1 Diagnosis,  Prevention, Treatment

  Prevention (including education & administration)
  Diagnosis and Treatment

                   Sub-Total
/ Research
1 Training
Facilities

n & administration)

Sub-Total

Training
Facilities

TOTAL

+:    Current State of the Art
i0:   Advanced State of the Art
ic**  Attributable to renal disease associated with hypertension.


source,  See Chapter 6.

35a


Table II

TOTAL COST SUMWRY
   ($1,000)

I
I          Kidney Disease Categories     Ii     Total

Xagnosis,  Prevention, Treatment
Prevention (including education 6 administration)
Diagnosis and Treatment

                  Sub-Total

iesearch
Iraining
Facilities

185,245 1 76.73

reYentlOn Lnc
iagnosis and T

Sub-Total

xsearch
Training
'dcilities

DlaEnosis and Treatment

wsearch
Training
rjcilities

                    TOTAL             i89,013    31,830          75,441

:>Lcelerated Exwnditure Level-1975f*
%gmsis, Prevention, Treatment                       200,000-vaccine
Prevention (including education b administration)
~Wwsis and Treatment

Sub-Total

'rsaarch
rrdining
hcilities

  Current State of the Art
  Advanced State of the Art
--' Attributable to renal disease associated with hypertension.

:r:e;  See Chapter 6.

35b


-

--                    -
         Kidney Disease Categories

Infectious    Hypersensitivity




        I

     70 Deaths      610 Deaths
3,231,260 Cases        -
15,962,420 Days       -

~c~g-Te=~ Benefit-Reductions:

Short-Term Benefit-Reductions:

Nortality
Prevalence
Morbid Days
Long-Term Benefit-Reductions:
Annual
Cumulative

     70 Deaths
3,243,&O Cases
16,273,640 Days



   1,770 Deaths
  26,190 Deaths

Accelerated    Exoenditure Level*
Short-Term Benefit-Reductions:

Mortality                        70 Deaths
Prevalence                 3,292,860 Cases
Morbid Days               17,483,ggO Days
Long-Term Benefit-Reductions:
Annual >-                 1,873 Deaths
Cumulative                   27,480 Deaths

Accelerated Exoenditure Level-1975$+
Short-Term Benefit-Reductions: !

Mortality
Pt-eV.?.lellCe
Morbid Days

     80 Deaths      770 Deaths
5.630. 780 cases     62,250 Cases
26,064,430 Days   2,610,OOO Days

Long-Term Benefit-Reductions:   I

Annual
Cumulative

Y,,ZS Deaths
76,500 Deaths

*    Current State of the Art
c*   Advanced State of the Art
**  Renal disease associated with hypertension.

Source :  See Chapter 6.

610 Deaths

-
-

610 Deaths

8,610 Deaths
320,000 Deaths

  2,190 Deaths
27,000 Cases
A,t~02,000 Days

4,330 Deaths
86,560 Deaths

  1,110 Deaths
34,880 cases
2,056,820 Days

4,820 Deaths
96.300 Deaths

  2,380 Deaths
42,750 Cases
2,:111,340 Days

4,820 Deaths
96,300 De'sths

  9,300 Deaths
289,690 Cases
5,578,860 Days

9,480 Deaths
:X9,660 Deaths

End-Stage

NO Deaths
-

I.560 Deaths

-

1.615 Deaths

17 399 Deaths

--
-

   3560 Deaths
3,258,260 cases
L7,764,420 Days

6,080 Deaths
112,410 Deaths

-

   `AS10 Deaths
3,278,740 Cases
18,330,460 Days

6,590 Deaths
122.490 Deaths

  10,735 kaths
3,335,610 Cases
19,795,220 Days

6,690 ikzaths
123.780 Deaths

37.5Yp Deaths i
5,991,723 Cases  1
34,253,290 Days

21,090 Deaths
586,160 Deaths ,

Short-term benefits - reduction in annual mortality, etc., when program is fully operative.

Long-term annual benefits - eventual annual reduction in number of cases reaching end-stage kidney disease.

Long-term cumulative benefits - sum total of long-term annual benefits.

35c


I  (53.8%) (25)

y APreventionl

Treatment
(25.6%)
(30) \

I Research
(31%) (36)                      I

Current   HEW Exuenditure Level

(Current State of'the Art)
Total Cost = 46.7*($1,000,000)

Facilities

Intermediate HEW Expenditure Level
  (Current State of the Art)       Prevention      \
Total Cost = 117.4*($1,000,000)    X7.9%)\

*

Totals are subject to rounding errors.

Fig, :.$ HEW Cost Summary.

Accelerated HEW Expenditure Level
(Current State of the Art)
Total Cost = 289.9*($1,000,000)

a

nd
(66


r
         Treatment

-. *.     (276.22%)
   5. *.   (185.2)

Facilities

       Prevention and Treatment
       (204.3) (304.59%)
\

Current  Total Expenditure Level
(Current State of the Art)
Total Cost = 241.5~~($1,000,000)

Trai
(8.1)

-/r Totals are subject to
  rounding errors.

Fig. 2.  Total Cost Summary

and Treatment
(266.14%)

Treatment
(215.9) (233.74%)

Prevention
  (245.8)

Prevention *\.

\ (43.2)
(46.76%

Treatment

Intermediate Total Expenditure Level
   (Current State of the Art)
Total Cost = 322.6*($1,OOO,UOO)

Accelerated 'liiYa1 ExpeMiture Level
(Current State of the Art)
Total Cost - 526.0*($1,000.000)


36

be large.  As the level of expenditure is liberalized this relationship

becomes reversed, although in each case the absolute expenditure for

  each component still grows.


C.  Future Shifting Proportions of Program Components

Figures 1 and 2 have illustrated the influence of the amount of avail-

able funds on the relative proportions of the various program components

in such total efforts.  Another factor which will influence these proportions

very significantly is the prevailing state of the art with respect to the

various primary ,kidney diseases and end-stage kidney failure.  This was

evident in the program analyses involving the individual groups of kidney

diseases; the same principle holds in relation to overall programs as

illustrated on Tables I and II.  Here too, the total program mixes illus-

trated do not and should not represent static proportions to be followed in

future years.  Depending on advances in knowledge and methodology which will

be derived from ongoing research efforts, these proportions will have to be
changed each year to obtain maximal benefits in terms of lives saved both in

the long run and in terms of the immediate future.  Thus, as rsurvival figures

for transplantation improve, more patients who would otherwise be maintained
Permanently with the aid of dialysis will be treated by kidne.y transplant,
and proportionately more funds should be channeled in this direction. As
improved methods of primary prevention are developed (such as an anti-

StreptococcaI vaccine) more funds will have to be allocated for the
applications of the new techniques since their successful use will reduce
the long-term mortality at a relatively small per capita expense.

D.  Outlook

With an advancing state of knowledge and with the passage

ProPortions of the optimal mix for a total program for the so

of


lut

ion or

time, the


37

amelioration of the kidney problem will follow the general outlines of

the diagram presented in Figure 3.  It illustrates a gradually increasing

emphasis on successful prevention and effective treatment of the various

primary kidney diseases with progressively lesser needs for the saving

of lives due to end-stage kidney disease.  Given such a set of circumstances

there will be a continued need for a repeated searching re-evaluation of

the entire kidney disease problem, so that program decisions will

continue to bring maximum benefits to patients afflicted with kidney disease,


Treatment
  of
End-Stage
Kidney
Disease

Prevention
    &
Treatment
   of
Primary;
Kidney
Diseases

   P-L_*----

-eases
T/

Figure 3.  EFFECT OF ADVANCING STATE OF THE ART ON FUTURE PROGRAM
      COMPOSITION

(Percentages are wholly arbitrary and merely serve to
illustrate shifting trends.)

37a


Chapter 2

`ci
rr L.

Kidney Disease--Current Status

I.   INTRODUCTION

    Dramatic advances in the treatment of end -stage  renal failure have

sparked new hope for people suffering from this hitherto fatal condition.

Today hundreds are living useful and productive lives while undergoing chronic

hemodialysis.  Hundreds more have received successfully transplanted human

kidneys and carry on life with minimal interruption in their daily activities.

Current programs to increase research and development in transplantation and

chronic hemodialysis, and training of personnel to supervise these complex

procedures promise a wider application.

  Yet, though dramatic and usually successful, chronic hemodialysis and

renal transplantation are difficult procedures  associated with considerable

morbidity and mortality.  At best these procedures are now applicable to a

relative few patients who reach the terminal stages of renal failure.

   A rational program in kidney disease, therefore, requires that oppor-

tunities to interrupt all processes leading to renal disease be sought and

pursued vigorously.  We must fill the gaps in our understanding of the path-

ogenesis of renal disease; we must define and isolate the etiologic factors,

and careful and detailed study must settle the areas of controversy.

II.   THE DISEASE PROBLEM

   As indicated in Chapter 1, diseases of the kidney have steadily gained

in significance as an area of social importance for both federal and nonfederal

research and service efforts during the last five years--primarily because

of the development of hemodialysis and kidney transplantation.  In general,


23

i,owever, mortality from kidney disease and other urinary system diseases
:?,a steadily declined since 1900 from about 100 deaths per 100,000 population

;., 1900 to 17.2 in 1964.  Total mortality for all age groups among the four

disease groups mentioned in Chapter 1 for 1964 was 58,788. The distribution

Sf mortality among these disease groups is. depicted in Figure 1.  As can be



seen, hypertensive renal cardiovascular diseases accounted for the great&St

?ercentage (36%) of deaths among the kidney disease groups considered in the

analysis.

Figures 2-5 graphically present the importance of morbidity associated

with kidney diseases in terms of prevalence, days of restricted activity, days

of bed disability and total work loss days.  In general,  there is little

morbidity associated with hypersensitivity diseases of the kidney.  Total morbid

time of all types is generally evenly distributed among the'remaining disease


groups.  During the period of July 1964 - June 1965, kidney diseases accounted

for about 140,000,000 total days of restricted activity, 63,500,OOO days of

bed disability, 17,000,OOO work loss days, with a prevalence of about 7,800,OOO



cases.

III.  DISEASES OF INTEREST

A.  Hypertension


   1.  Introduction

    Arterial blood pressure is maintained by a variety of mechanisms

  and is subject to a number of influences such as posture, emotional

   state and exercise.  When measured correctly in the steady resting state

  a diastolic blood pressure in excess of 9Omm. of mercury is considered

abnormal.

The conditions characterized by established diastolic hypertension


Hypersensitivity

IV.  Other Diseases of
    The Kidney

15,187
25.8%

III.  Hypertensive Renal
     Cardiovascular
        Diseases

20,890
35.6%

Total Mortality--58,788

Pig. 1.  Mortality from Kidney Disease in 1964 by Disease Group.

Source:  Unpublished data from the U.S. Department of Health, Education, and
     Welfare, Public Health Service, National Center for Health Statistics,
    Washington, D.C.

39a


/ II.
  II.  Hypersensitivity Diseases
     Hypersensitivity Diseases


             104
             1.3%

"I
III.  Hypertensive Renal
      Cardiovascular
         Diseases



          35.1%

Infectious Diseases



    24.7%

Other Diseases of the Kidney

Total Prevalence - 7,847

Fig. 2.  Selected Chronic Conditions, Prevalence (1000's), United States,
     July 1964 - June 1965.

Source:  For civilian non-institutional population from unpublished data
       from the U.S. Department of Health, Education, and Welfare,
     Public Health Service, National Center for Health Statistics,
     Washington, D.C.

39b


, II.  Hypersensitivity

37,610
26.9%

III.  Hypertensive Renal
      Cardiovascular
        Diseases

        44.138

   IV.  Other Diseases of the Kidney
\-      54,180
               38.7%

Total Days of Restricted Activity - 139,939

Fig. 3.  Selected Chronic Conditions, Days of Restricted Activity
     (1000's), United States, July 1964 - June 1965.

Source:  For Civilian non-institutional population from unpublished data
    from the U.S. Department of Health, Education, and Welfare,
     Public Health Service National Center Ear Health Statistics,
      Washington, D.C.

39c


/ II.  Hypersensitivity Diseases

Infectious Diseases

17,012

Hypertensive Renal
Cardiovascular \

Total Days of Bed Disability - 63,494

9ig. 4.  Selected Chronic Conditions, Days of Bed Disability (1000's),
      United States, July 1964 - June 1965.

Source:  For civilian non-institutional population from unpublished data
    from the U.S. Department of Health, Education, and Welfare,
     Public Health Service, National Center for Health Statistics,
     Washington, D.C.

39d


, II.  Hypersensitivity Diseases

765
4.6%

/                                 III.  Hypertensive
                                      Renal
   I.  Infectious Diseases

Fig. 5.

Source:

IV.  Other Diseases of the Kidney

9,459
56.5%

Total Work Loss Days - 16,729

Selected Chronic Conditions, Work Loss Days (1000's), United
States, July 1964 - June 1965.

For civilian non-institutional population from unpublished data
from the U.S. Department of Health, Education, and Welfare,
Public Health Service, National Center for Health Statistics,
Washington, D.C.

39e


include primary (essential) hypertension, of unknown cause, comprising

80-90% of the total, and secondary hypertension accounting for lo--20%

of the hypertensive population.  In the secondary group, the hyperten-

sion can be traced to some underlying process.  This group is especially

important because often the hypertension can be cured.  Processes leading

to secondary hypertension include:  adrenal tumors, renal artery stenosis,

pyeicnephritis, acute and chronic glomerulonephritis, pheochromocytoma,

coarctation of the aorta, and certain disorders of the central ner~us system.


2.  Primary (Essential) Hypertension



    a.   Incidence

     Primary hypertension occurs in 5-10% of the adult population

   of the United States.  In 1965 it was estimated that 9,200,OOO

  individuals had hypertension.   It is twice as common in women as in


   men and t-here is a strong familial tendency.  The average age of

   detection is about 32 and onset after 50 years of age is most


   unusual.  When followed from the onset of hypertension, the average

  patient lives for a period of 20 years.  (The average life expect-

  ancy at 32 is 41.5 years.)  The course of the individual patient


   varies.  Some patients may enter an accelerated phase in a few months;

  others may survive with few complications fcr 40 or more years.

    Of those with essential hypertension 5-10% develop an accelerated

  or malignant form which is fatal if untreated.


   b.  Clinical Course--Benign Hypertension

    Initially there may be no symptoms and the patient is often

  unaware of the illness until informed by his physician.  The clinical

  course roughly divided into an uncomplicated phase lasting an aver<W"

  of 15 years and a complicated phase with progressive damage to the

heart, kidneys, brain, eyes, and other systems.


  During the uncomplicated phase about 2/3 o.f the patients have

a variety of usually minor symptoms including fatigue, nervousness

and headaches.  After an indefinite period, complications appear.

Atherosclerosis is common.  Hypertension accelerates arterial damage

and predisposes to the deposition of lipid materials.  In most there

is gradual enlargement of the heart.  Congestive heart failure is

eventually responsible for about 25% of the deaths and is a contributing

factor in another 25%.  About 10% of hypertensives die of a myocardial

infarction while another 10% die following cerebral thrombosis or

hemorrhage.  Thus, some 70% die from major vascular problems.

  In the kidneys, damage to the.small arteries is found in a high

percentage-of patients.  Approximately one-half eventually develop

some evidence of renal damage (manifested by polyuria, diminished

concentrating power, or proteinuria),  but uremia is only rarely the

cause of death unless there is an accelerated or malignant phase of

disease.

c. Accelerated or Malignant Form

  Some 5-10% of patients with essential hypertension develop an

accelerated phase with progressive renal damage and higher fixed

diastolic blood pressure.  The onset is usually abrupt. and is

characterized by headaches, failing vision, nausea, and weight loss.

Unless the course is interrupted by treatment, complications develop

rapidly and death from brain, heart or kidne,y damage usually occurs

within two years.  About one-third of these patients die with severe

renal complications.  Early treatment of this group is important

since progressive changes in the small arteries of the kidney develop

rapidly.  After these changes have developed to an advanced state,


  !~~ering Slood pressure may precipitate renal failure.  Therapy

  started early significantly prolongs life in this group.  The impact

  of successful drug therapy for malignant hypertension can be inferred

  from an almost 50% decline in the death rate from hypertensive heart

  disease since the introduction of antihypertensive agents in 1952.

3.  Secondary Hypertension

  In every patient with established diastolic hypertension, the pos-

SiSility of secondary hypertension should be considered.   Known  2 .?'L-L; e;

must be systematically excluded by history, physical examination, I
                                                              a2>ro-

-riate laboratory tests and X-rays.
$2                       The incidence of secondary h:;per-

fensions is estimated at from 10 to 20% of the total hypertensive popu-

lation.  Of these 5-15% are caused by renovascular (renal arterial) lesions.

Another group of potentially curable hypertensives are those having

hypertension secondary to aldosterone-producing adrenal tumors.  Presently

experts differ on the incidence of aldosterone-producing tumors in the

hypertensive population.  It is variously estimated that these tumors

account for from 1 to 20% of the hypertensive population.  Most ixvesti-

gators are now finding that 1% o f their hypertensive patients have this


condition.  Other causes of secondary hypertension such as coarctation of

the aorta, various renal diseases, Cushing's disease, pheochromocytoma and

central nervous system disorders can be excluded only by careful and often

extensive examination.

4.  Etiology of Primary Hypertension

  The cause or caases of hypertension have been dnd are t

                                              he sub 'ject

of' intensive study by many distinguished investigators.  They-- are three


major theories relating to the development of hypertension.   Some have

stressed the importance of neurogenic factors and psychologic stress?


others have emphasized.excessive sodium intake and abnormal endocrine

control, while still others have concluded that renal circulation and

renin are of primary importance in the development of hypertension.

There is much'evidence supporting each theory. Possibly one or all of

these factors operates in a given individual who may be genetically pre-

disposed to the development of hypertension.  In this brief review emphasis
will be placed on the renal relationships with hypertension without intending
to imply that renal factors are the underlying cause of all primary hyper-

tension.

The association between pyelonephritis and hypertension exists but

the exact nature of the relationship has not been clarified.  Patients

with hypertension have a reported incidence of pyelonephritis varying

from 14% to 51%.  Conversely, from 12% to 85% of patients with histologic

evidence of pyelonephritis are reported as having hypertension.  The high

incidence of pyelqnephritic kidneys in hypertensives suggests that hyper-

tension either predisposes to renal infection or is the direct cause of

pathologic changes which are indistinguishable from those usually caused

by infection.  It has also been postulated that chronic renal infection is

a major cause of hypertension.  Current evidence is substantial regarding

these views, but is not yet conclusive.

The relationship between hypertension and arteriolar nephrosclerosis
(damage to the small arteries of the kidney), of the kidneys is also a subjc

of continuing controversy.  Clearly, most hypertensives have nephrosclerosi

to a greater or lesser extent.  Now most investigators think that the

nephrosclerosis is secondary to the hypertension.  Some, however, maintain

that the renal arteriolar lesions may be ths pr:cipitating cause of the

hypertension.  Whatever the underlying cause, it seems clear that once


44

established, hypertension accelerates the development of renal arteriolar

stenosis and conversely that the arteriolar lesions may sustain and

aggravate the increase in blood pressure.  In malignant hlypertension, renal

ischemia leads to increased renin output with secondary hyperaldosteronism

and an accelerated rate of hypertension which in turn leads to further

renal arteriolar damage.

Further clarification of these important areas will have far-reaching

therapeutic implications.


5.  Management of Hypertension

  With proper screening of the hypertensive population it is probable

that lo-20% will be found to have underlying causes amenable to permanent


cure.  In malignant hypertension and in advanced diastolic hypertension

(blood pressures in excess of 1lOmm. in men and 12Omm. in women) early

drug therapy and dietary management have been demonstrated sharply to

reduce morbidity and mortality.  In patients with lesser elevations of

blood pressure the evidence favoring treatment is less substantial.   Treat-

ment must be individualized balancing the risks inherent in any chronic

  treatment against the potential benefits.  Current long-term studies will

  help clarify this area.


B.  Pyelonephritis and Infections of the Kidney

During the past 30 years since the reports of Longcope and Winkenwerder,

and Weiss and Parker, the term pyelonephritis has been widely used to imply

a pathologic process resulting from the immediate or late effects of bacterial

infection of the kidneys.  Unfortunately, the criteria used to diagnose pyelo-

nephritis are not uniform.

1.  Incidence

  The incidence of chronic pyelonephritis varies widely among various


autopsy series from.as low as 2% to as high as 35%.  Reasons for these
differences are the varying criteria used by pathologists to diagnose

pyelonephritis and the differing populations studied. Kidney infections

are more common in older populations, are more frequent in Negroes, and
                                                        

occur in higher incidence among lower socio-economic groups.  In one



careful study, pyelonephritis was found in 3.3% of 4,596 autopsies.  hlY

10% of these cases of pyelonephritis had demonstrable bacteriuria at death

although previous treatment may have resulted in eradication of bacteria

in some cases.  In this same series 1.6% of 4:,596 deaths were attributed

to uremia.  In another study acute and chronic pyelonephritis was found

in 10% to 20% of the autopsies at two hospitals but was judged to be a

major factor causing death in only one-third of these cases.

On a national basis in 1964, about 10,000 of the 1,800,OOO deaths or

0.5% were attributed to infections of the kidney. This figure must be

analyzed.  It represents 'data from a wide variety of sources where there

are considerable differences in the diagnostic criteria of pyelonephritis.
It does not include cases of obstructive uropathy due to prostatic hyper-
trophy and prostatic cancer when these were ruled the underlying cause
of death though renal infection may have precipitated death.  On the other

hand, this figure includes cases of renal disease in which there was no

documentation of infection by bacteriologic or pathologic means. In other

cases renal infection may have been recognized, but the underlying urologic

or metabolic defect may not have been apparent.

  Such incidence data of kidney infection and pyelonephritis must,
therefore, be approached with caution in program planning.  The final

diagnosis of the cause of death is at best a good interpretation of events

in the current state of the art.  Many cases of infection are certainly


missed and others are classified erroneously as infection.  The margin

of error is unknown, but could be large.  A rational approach to the

control of pyelonephritis must include further research into all causes

of chronic interstitial nephritis  as well as the search for methods to

control kidney infection.


2.  Acute Fyslonephritis

  Acute pyelonephritis is a common problem usually caused by g-am

negative bacterial invasion of the kidney.  The onset is usually abrupt


bi i t b characteristic symptoms although at times clinical symptoms may be

subtle or absent.  The acute symptoms generally subside rapidly although

bacteriuria may persist without adequate treatment.  Recurrences are common,

particularly during and following pregnancy.  In recurrent cases, a careful

search for underlying predisposing factors such as prostatic hypertrophy,


stones, diabetes mellitus and congenital malformations should .be made.

Remedial procedures are indicated where feasible.


3.  Chronic Pyelonephritis

  Symptoms of infection are frequently absent in patients with chronic

pyelonephritis although there may be a history of previous urinary tract


infection.  The onset is usually insidious with gradual development of

the manifestations of chronic renal failure.  This period of relative renal

insufficiency may be long.  During this perLod many patients Eve in

comfort for years despite azotemia.  Sacteriuria may be absent or present

only intermittently making accurate diagnosis difficult during life.

In such cases, other causes of nephritis must be considered.  liven tually,

end-stage renal failure is reached unless intervention is undertaken.


4.  Bacteriuria and Urinary Tract Infection

  Bacteriuria may be defined as the presence of over 100,000 organisms

per cc.  of urine on a culture of clean fresh urine.  Defined in this

manner persistent bacteriuria indicates infection of the urinary tract.

There has been much debate about the role of bacterial infection in the

pathogenesis of chronic pyelonephritis.  Repeated bouts of kidney infection

whether manifest or silent lead to renal scarring and eventual renal

failure.  But in many cases bacteria cannot be isolated from kidneys in

which the pathologic diagnosis is pyelonephritis.  One current and

controversial theory to explain this discrepancy is that bacteria may

initiate a self-sustaining destructive process which persists after

bacteria have been eradicated.  Another possibility is that some cases

classified as pyelonephritis are due to non-bacterial causes.   It is not

known how often bacteriuria per se is the forerunner of chronic pyelo-

nephritis.  Since bacteriuria is present in patients who do not subsequently

develop pyelonephritis and since the source of bacteria may be the

urethra, bladder or other lower urinary tract sites, there must be many

cases in which ascending infection does not develop.  On the other hand,

bacteria in the lower urinary tract may lead to kidney infection, parti-

cularly in the presence of predisposing factors such as obstruction,

stones, diabetes and gout.  Furthermore,  such bacterial infection can act

as a source of virulent organisms in the development of septicemia.  Thuc.

while bacteriuria may not always lead to the development of chronic

pyelonephritis, its presence should be taken seriously, and careful

consideration given to management.


   In young patients persistence of bacteriuria should be confirmed

by a minimum of two cultures of clean voided specimens.   If bacteriuria

persists in an asymptomatic patient,  a short course of antibiotic treat-

ment should be followed with repeat culture at intervals.  If bacteriuria

still persists, investigation to detect underlying correctable lesions is


indicated.

   In later stages of pregnancy about 6% have asymptomatic bacteriuria.

Of these, at least 40% will develop pyelonephritis.   It seems reasonable

to treat bacteriuric pregnant women for the duration of the pregnancy.

In older patients in whom the incidence of bacteriuria may be 10 to 20%,

treatment must be undertaken with some caution.  The eradication of

bacteriuria in the elderly is difficult and the risk of complications

from over-zealous treatment seems great.

   Carefully controlled long-term studies are necessary to determine

in which cases vigorous treatment of bacteriuria will prevent the develop-

ment of chronic pyelonephritis.  Judicious application of current techniques

to control infection may  result in eventual reduction in the number

reaching the end-stages of pyelonephritis.

Hypersensitivity Diseases


1.  Acute Glomerulonephritis

  Acute glomerulonephritis is a common disease affecting all age groups,

but it occurs predominantly in children.  Almost all cases follow by one

to four weeks infection with hemolytic streptococci.   These bacteria

initiate an immune process which is almost certainly responsible for the

subsequent renal damage.  Only certain nephritogenic types of streptococci

are responsible for acute glomerulonephritis.  Thus, in some epidemics

of hemolytic streptococcal infections, glomerulonephritis is not seen,


4s

while in others the attack rate is high, the disease.often striking

several members'of the same family.

  Most cases are mild and some may go unnoticed.  In mild symptomatic


cases, renal damage is manifested by blood in the urine and puffiness

due to salt and water retention.  In more severe cases hypertension,

anemia, and even acute renal failure may develop.  As a rule most patients

recover completely,but currently, about 2% of hospitalized patients die


of acute renal failure.  In 1964, 585 deaths were attributed to acute

nephritis.  An additional 2,900 died of nephritis not specified as acute

or chronic.  A few patients with the acute form enter a protracted subacute

course with gradual deterioration of renal function over a 6 to 12 month

period.  Nephrosis seldom occurs in the acute phase.

  In another group, comprising probably not much more than 1% of the

total with acute post streptococcal glomerulonephritis, healing is incom-

plete.  These patients show continuing proteinuria and eventually develop

one type of chronic glomerulonephritis.  Failure to heal is more common

in adult cases of acute glomerulonephritis and iseems to be associated

with non-epidemic streptococcal infections.  Estimates vary, but about

one-tenth to one-third of all cases of chronic glomerulonephritis are

post streptococcal in nature.


2.  Chronic Glomerulonephritis

  Chronic nephritis and nephrosis accounted for 8,800 deaths in 1964.

Chronic glomerulonephritis cannot be defined as a single disease entity

and probably has multiple causes.   In most cases the etiology is obscure.

In various autopsy series its frequency has been reported from 0.5% to

1.5% and is about one-third as frequent a cause of death as pyelonephritis.

The onset occurs in all age groups.  If those presenting with the nephrotic


syndrome are excluded, the greatest number are first noted between age

10 and 40.

  Chronic glomerulonephritis usually begins quietly and progresses

slowly.  The first manifestation is frequently persistent protein in the


urine.  In other instances onset is abrupt with rapid development of

nephrotic syndrome characterized by edema and massive proteinuria.  Hyper-

tension rarely appears until renal damage is severe.  The course is variable

lasting from one to about forty years.  In one series the average duration

was seven and one-half years in those who have died, however, many in

this series are still living.  The course may be punctuated by episodes

of nephrosis and may terminate abruptly.  Signs of renal failure appear

gradually, but once azotemia appears, progress to end-stage renal f.ailure

is usually a matter of only a few years.


3.  Nephrotic Syndrome

  Massive loss of protein in the urine may be caused by a variety of

renal diseases and leads to the development of the nephrotic syndrome.

Clinically this syndrome is characterized by massive swelling of the

body and face known as generalized edema. Underlying renal diseases such

as lupus erythematosus, diabetic nephropathy and post streptococcal glomer-

ulonephritis are occassionally recognized, but more often no underlying

cause can be detected.


4.  Idiopathic Nephrotic Syndrome

  Nephrotic syndrome due to unknown causes is a major cause of morbidity

and mortality, most often in children between the ages of one and six.

The annual occurrence in this age group is estimated at 2 per 100,000.

  Patients with the nephrotic syndrome present a variety of clinical

pictures.  In the idiopathic form glomerular lesions lead to urinary



52

protein loss with the development of generalized edema. Complications in

severe cases include hypertension, malnutrition, anemia, infection and

occasional vascular collapse.  In children, about one-third heal spontane-

ously .  Recently corticosteroid therapy and careful management appear

to have improved survival rates.  In adults with this disorder, the out-

look is even more serious.  Spontaneous healing is not common and progressive

renal failure usually ensues.

5.  Pathogenesis of Nephrotic Syndrome and Chronic Glomerulonephritis

  The underly'ing causes of these renal diseases are not known. There

is much evidence to indicate that immune mechanisms are responsible, but

the precise sequence of events is not clear.  The application of safe

biopsy techniques, sophisticated biochemical methods and electron micro-

scopy to the study of glomerular lesions has helped unravel this complex

group of disorders.  The application of new immunological concep.ts,.combined

with transplantation studies may finally yield answers to the remaining

basic questions about these diseases.

6.  Lupus Nephritis

  Systemic lupus erythematosus is a generalized disease involving

the kidneys, brain, lungs, skin, joints, and other organs. Nearly 300

deaths were listed in 1964.  It is predominantly a disease of young women,

but attacks both sexes through a wide age range.   The incidence has

increased markedly during the past two decades partly because of improved
methods of diagnosis and almost certainly.because of the more widespread

use of sensitizing drugs.  There is much evidence that an abnormal immune

response, precipitated by a variety of agents, is responsible for this

disease.


                               52

  Renal involvement in patients with systemic lupus erythematosus is

perhaps the most ominous of the many manifestations of the disease, In

general, renal involvement is found in about two-thirds of lupus patients.

Patients who exhibit renal involvement usually do so early in the course of

their disease.  The renal lesions run the gamut from a local glomerulitis

involving parts of glomeruli, to a focal lesion involving some glomeruli,
to generalized subacute or chronic glomerulonephritis, with or without

the characteristic wire-loop lesion.

  Clinical manifestations of renal lupus include hypertension, edema,

and on occasion oliguria or anuria with rapidly progressing uremia.  M=Y

patients with lupus nephritis show at some stage the nephrotic syndrome.

Usually, this group does poorly.

  Corticosteroids have become a mainstay of lupus nephritis therapy,

though there are divergent opinions as to the effectiveness of these

drugs in various stages of the disease.  Recently antimetabolites have

heen used and present information suggests a significant measure of success.

Additional information about the nature of the renal changes in this

disease has been obtained by attempts to relate ultrastructure and functional

derangements.  Studies are under way to elucidate the role played by plasma

proteins in the evolution of this disease.  Important work is being done

correlating the histologic changes in the kidney with clinical course.

Understanding of the pathogenesis of this disease has important implications

for all hypersensitivity diseases such as rheumatoid arthritis, all chronic

nephritis and rheumatic fever and has relativity to transplantation

immunology.


                                  53

D.  Other Related Renal Diseases

  Many kidney diseases and other diseases which often lead to severe renal

disease were not included in this initial analysis.  These are described

briefly in this section.

   1.  Polycystic Disease of the Kidneys

    This disease is by far the most important of the developmental

  anomalies of the kidneys.  This anomaly was held responsible for 1,061

  deaths in the United States in 1964.  In this group over three-fourths

of the deaths occurred before the age of 60.  This disease masquerades

in a variety of forms including vascular accidents, hypertension, pyelo-

nephritis and chronic renal failure.   There are two forms:   one inherited

as a dominant trait which usually becomes manifest in adult patients, and

one which appears to be inherited as a recessive trait primarily mani-

fested in children.  A history of polycystic disease is usually readily

obtained in other family members; unfortunately in some families there

is a pathetic desire to hide the trait.  Conventional treatment helps

these patients.  But, as end-stage renal failure approaches, hemodialysis

and eventual renal transplantation are their only hope for survival.

2.  Gouty Nephropathy

  An estimated 250,000 people in this country are suffering from some

form of gout.  In 1964, 130 deaths were attributed to gout.   In the

advanced stages of gout one of the major causes of death is renal insufficient)

Some reports suggest that albuminuria occurs in up to 40% of patients with

gout, renal calculi in 17% and that the development of renal insufficiency

in 18% of cases.  The only distinctive pathologic feature of the gouty

kidney is the presence of urate crystals. The precipitation of this

material in the kidney may be responsible for the frequently observed


pathologic picture of pyelonephritis or nephrosclerosis and less often

amyloidosis.

Management of gout has until recently been limited to the relief

of joint symptoms primarily through the use of colchicine and the

reduction of elevated blood uric acid levels by increasing uric acid

excretion primarily through the use of probenecid.  A new approach to

reduction of blood uric acid levels has been provided by the introduction

of allopurinol, a xanthine oxidase inhibitor, which acts by decreasing

the production rather than the excretion of uric acid.  Important avenues

of investigation have been opened not only in primary gout but in other

diseases associated with increased uric acid levels.  The promise of

reduction in morbidity and mortality from gout is great.

3.  Hypercalcemia

  Hypercalcemia from a variety of causes may produce secondary renal

disease which if uninterrupted is often lethal.   Calcification of the

kidney tissue, formation of stones, and secondary pyelonephritis are

common in advanced cases and usually lead to end-stage renal failure.

Such diverse entities as hyperparathyroidism, sarcoidosis, vitamin D

intoxication, excessive ingestion of milk and alkali, and immobilization

in bed can lead to hypercalcemic nephropathy.  In many of these cases

therapy directed at the underlying problem is successful in arresting

the progress of renal damage.  Often, however, the process is not recog-

nized until renal damage has progressed to an advanced state.  In this

stage, particularly if hypertension has supervened, reversal of the

process is usually impossible and terminal renal failure ensues.


                                                                           _
                                r&
4.  Diabetes

  AS the life span of diabetics has increased, renal disease has become

an increasingly important cause of morbidity and mortality.  The renal

complications of diabetes are manifold and include acute and chronic

infection, renal arterio-sclerosis and arteriolar sclerosis with hyper-

tension, and finally intercapillary glomerulosclerosis, a process seen

only in association with diabetes mellitus.  Renal diseases account for

over 10% of the deaths in diabetics.

  The management of these renal problems is only moderately successful.

Eradication of urinary tract infection is particularly difficult in

diabetics, but should be pursued with vigor since this may retard the

progress of renal damage and prevent septicemia.  Hypertension may be

ameliorated by conventional therapy.

  Unfortunately, chronic hemodialysis and transplantation offer little

chance for long-term survival in most of these patients since severe

arterial disease is usually widespread in affected patients.   Better

understanding of the mechanisms of development of atherosclerosis and of

lipid metabolism and changes occurring in the capillary basement membrane

offer the best hope for improving the outlook of these patients.

5.  Miscellaneous Renal and Renal Related Diseases

  Many other diseases are of importance in any discussion of kidney


diseases.  Malignant diseases of the  p
                                --   rostate  account for over 15,000

deaths annually.  In this usually indolent malignancy early detection

may cure many patients, while hormonal therapy will help others.  Prompt

treatment of renal infections and alleviation of urinary obstruction


reduces renal deaths.  Benign prostatic hypertrophy leads to urinary tract

obstruction with frequent development of hydronephrosis and pyelonephritis.


New cryOSUrgiCa1 teChaiq.ucs are promising for this group and there
      f

is indication that hormonal therapy may be beneficial.
Kidney Stones often lead to obstruction and/infection.   In cases

due to gout and hypercalcemia the treatment of the underlying disorder may

be effective.  In other cases the cause is not clear, but may be related

to individual habits or peculiarities of the environment.  Recent

identification and isolation of an "anti-stone substance" which is absent

in the urine of some who develop kidney stones may lead to new therapeutic

methods.  In still other cases, such as cystinuria and oxalosis, the
metabolic defects have been identified and corrective therapy may be forth-

coming.

    A number of urinary tract anomalies are lethal in infancy.  Other

  obstructive and muscular lesions may respond to treatment in later life.

    Tuberculosis of the genitourinary tract still accounts for almost

  100 deaths per year and if recognized may respond to a variety of measures.

  Toxemias of pregnancy still account for over 200 deaths per year.  Renal

  amyloidosis secondary to rheumatoid arthritis, ulcerative colitis and

  leprosy accounts for many deaths.  Amyloidosis of the kidney due to

  chronic infectious diseases is a major world cause of renal deaths.


E.  Acute Renal Failure

Acute renal failure may appear suddenly following a massive kidney Injury
of develop in the course of a chronic renal disease.  In either case urine

flow is greatly diminished and the kidneys are temporarily unable to perform

their usual functions.  The incidence of acute renal failure is difficult to

determine, however, in one university referral center, acute renal failure

accounted for half of the patients seen with uremia.  In a nationwide sample


the proportion of patients with uremia who present with acute renal failure

would probably be much lower.

Acute renal failure may be due to a number of causes including insufficient

renal blood flow, transfusion reactions from mis-matched blood, fulminating

infections, kidney poisons, acute urinary tract obstruction and acute

glomerulonephritis.  Prompt restoration of blood flow, relief of obstruction

and effective treatment of infection are essential in preventing further

renal damage.  Toxic substances must be immediately identified and measures

taken to remove them by dialysis or chemical binding whenever possible.

  After all available measures have been taken to arrest further damage,
assessment of the degree of damage must be undertaken and management planned.

In a few cases the damage is mild and no further measures are necessary. In

others, renal function ceases completely and the patients must be sustained

by a combination of dialysis and dietary regulation while healing takes place.

In these cases after a period of days or weeks the kidney gradually resumes

its function and may eventually show return to normal function.

  Broad advances in our knowledge of kidney function, wide use of hemo-

dialysis and availability of remarkable new therapeutic agents have resulted

in a gradual increase in the number of patients surviving.  Now over 50% of

patients with severe acute renal failure recover.

  In other patients kidney damage is too severe and effective renal function

does not return.  Some die of other underlying processes or infection while

others have little or no return of function and enter a period of chronic renal


failure.

F.  Chronic Renal Failure

Despite current screening programs and early medical intervention in

many cases of renal diseases, many patients do not seek medical attention


Llntil irreversible renal damage has progressed to an advanced state.  Often

d,,tructive kidney lesions are painless and indeed asymptomatic. Symptoms
3aY not be noticed by the patient until 50 to 80% of his kidneys have been

destroyed*  If at this point the patient seeks the help of his physician it

nay still be possible, depending on the underlying disease, to arrest renal

destruction, prolong life and reduce complications.  For example, in chronic

pyeIonephritis due to bacterial infection, relief of obstruction or removal

0f stones combined with selective antibiotic therapy may arrest renal destruction

and in lupus erythematosus steroid and immunosuppressive therapy often retard

the progress of renal destruction.  In other cases such as chronic

+merulonephritis, congenital polycystic disease, diabetic glomerulosclerosis,

and some cases of chronic pyelonephritis, there is no current effective therapy

to arrest renal destruction.

  '1.  Dietary Therapy

    In these cases careful intelligent management has much to offer.

  Three major kidney functions are the regulation of water and electrolytes,

  the excretion of nitrogenous waste products and the excretion of excess

   acid.  By careful regulation of dietary intake of sodium and potassium,

restriction of protein intake to a minimum balanced mixture of essential

amino acids,and limitation of the acid forming potential of the diet It

is possible to reduce considerably the morbidity of patients with chronic

renal failure.  In cooperative patients, the frequency of dialysis can be

greatly reduced.  Anemia, hypertension and certain metabolic disturbances

remain severe problems in some patients.

2.  Hemodialysis and Transplantation

In those patients who have progressed to the end-stages of renal

failure or who have other threatening complications which can no longer


be managed by selective management of intake, chronic hemodialysis and

renal transplantation now offer a new hope for survival.   Because

experience is limited,it is difficult to'predict the eventual applicability'

of these two procedures to the total population with end-stage renal

failure.  Further research into `improved dialysis membranes, combinations

of hemodialysis with various ion exchange methods and/or selective adsorpti&
                                                                           :

procedures, and better understanding of complex metabolic problems will

reduce the morbidity and mortality associated with hemodialysis and may ..
yield entirely new methods with wider application and reduced cost. Home -.

dialysis is promising.  In the field of- organ transplantation experience

in management of transplant recipients and improved matching of donor

kidney and recipient have resulted in substantial reduction in morbidity

and mortality.  Now this procedure is performed with remarkable success

in a number of centers.  Further advances in histocompatibility typing,

selective immunosuppression and patient management can be expected.

a.  Hemodialysis

  Hemodialysis has been used with success in acute renal failure

since 1947.  The development of the indwelling arteriovenous shunt

in 1960 made possible the use of intermittent hemodialysis to prolong

life in irreversible uremia.  In the current state of the art, a

number of problems are apparent in the application of this procedure.

b.  Factors Limiting Application of Hemodialysis

  Partly because of limited facilities and personnel and because

of ths limitations of current techniques, experience has largely

been limited to patients between ages 20 and 55. Unfortunately, about

three fourths of patients reaching end-stage renal failure and who

thus might benefit from hemodialysis are beyond the age of 60.


  Within the mid-age group, psychological problems have presented

a serious obstacle to some who might have benefited from hemodialysis.

A number of patients have developed problems in accepting their dependence

on dialysis machines and their attending medical personnel while

others have suffered a change in self image which has led to serious

social difficulties.  The motivation and intelligence of the patient


are crucial to success.

  The medical problems associated with chronic hemodialysis are

formidable.  Peripheral neuropathy and metastatic calcification are



common.  Hypertension is often difficult to control.  The anemia of

chronic renal failure often requires transfusions which eventually

may lead to hemosiderosis.  Serum hepatitis is a danger to the patient

and the attending personnel as well.  Infection at the cannula site

and clotting of the cannula are persistent problems.  Severe metabolic

bone disease is still frequent although some progress has been made

in its control.  Human errors and mechanical difficulties are occasionally

responsible for failures.  Well trained, highly motivated and experi-

enced medical personnel are scarce.

  Despite these problems many live useful, productive lives.   While

extension of hemodialysis to older age groups presents difficult

problems, technical improvements and increased experience may prove

intermittent hemodialysis feasible in some older patients.   Intermittent

hemodialysis combined with dietary therapy may prolong useful life in

many and sustain others who might benefit from renal transplantation.

  Clearly, many now face death who could be helped by intermittent

hemodialysis.


C.  Kidney Transplantation
    -

  Renal transplantation offers another future hope for those afflicted

with end-stage renal failure.  Currently 30-month survival rates range

from 17 to 47% for patients with cadaver transplants and 60% or more

for living related donors.  In cases where a good histocompatibility

match has been obtained and no rejection crisis has occurred in the

first few months after transplantation, good renal function has been

reported in up to 93% of patients after three and one-half years.

d.  Limitations

  Aside from the operative morbidity and mortality associated with

renal transplantation there are currently several major obstacles

to greater use of renal transplantation for end-stage renal failure.

The availability of viable human kidneys presents a major problem.

The use of living related donors raises serious moral questions and

such donors will provide only a limited number of kidneys.   Cadaver

kidneys are a major potential source of viable kidneys; however, the

problems of histocompatibility matching, the ethical and legal questions

of consent, and the logistical problems of preservation and trans-

portation have not yet been solved.  Immunosuppressive therapy has

been successful in preventing homograft rejection in many cases, but

has often led to serious and sometimes fatal infection in the recipient.

Although the development of more selective immunosuppressive agents

has been promising, the problem of complicating infections has not

been ovtrcome.

Large areas of investigation offering significant conceptual
advances in the field of tissue transplantation remain to be explored.
Induction of adult tolerance, detailed analysis of histocompatibility


antigens and work on the non-immunologic mechanisms of cell to cell

interaction are some of these.

e.  Peritoneal Dialysis

  Peritoneal dialysis offers a useful, but a present limited alternative

to hemodialysis.  Exchange of chemicals is less efficient, leading

to longer treatment periods than with hemodialysis, and infection

remains a major obstacle.  Intermittent catheterization, new flexible

catheters, and automated flushing have improved this method.

!-.  Poisoning

  In 1964, over 1,000 deaths resulted from accidental poisonings from

s;lIicylates, barbiturates and other analgesic and soporific agents.  In addition,

over 2,400 suicides resulted from use of these agents.  Hemodialysis techniques

.~re of great value in most of these poisonings and it is reasonable to assume

tllat a significant number of these deaths could have been avoided if personnel

trained in the techniques of emergency hemodialysis had been widely available.


1.

2.

3.

4.

5.

6.

7.

8.

9.





10.



11.





12.



13.

REFERENCES

"Annual Report of the General Clinical Research Centers", U. S. Public
Health Service, National Institutes of Health, 1967, (unpublished data).

Beeson, Paul B., and Walsh McDermott, eds., Textbook of Medicine,
Philadelphia: W. B. Saunders Co., 1963.

Combined Staff Clinic, "Recent Advances in Hypertension", American
Journal of Medicine, vol. 39 (1965) pp. 616-645.

Holme, Walsten, and Maeve O'Connor, eds.,#'Ethics in Medical Progress:
Ciba Foundation Symposium, Boston: Little, Brown, and Co., 1966.

Ingelfinger, Franz J., et al., eds., Controversy in Internal Medicine,
Philadelphia: W. B. Sauzers Company, 1966.

Kirkendall, Walter M., Annette E. Fitz, and Montague S. Lawrence,
"Renal Hypertension", The New England Journal of Medicine, 276:479,
March 2, 1967.

Kupfer, Sherman and Raul Goyo, '!A New,
Intermittent Peritoneal Dialysis:    Easily Inserted Catheter for
                         Journal of the American Medical
Association, 200:115, May 15, 1967.

Little, P. J. and H. E. de Wardener, "Acute Pyelonephritis", The Lancet,
p. 1277, December 10, 1966.

Metceff, Jack, ed., Proceedings of the Seventh Annual Conference on the
                                                                          --
Nephrotic Syndrome, New York: The National Nephrosis Foundation, Inc.,
1956.

Michael, Alfred J., et al., "Immunosuppressive Therapy of Chronic Renal
Disease", The New England Journal of Medicine, 276:~. 817, April 13, 1967.

Pawlowski, Joseph M., John W. Bloxdorf, and Paul Kimmelstiel, "Chronic
Pyelonephritis", The New England Journal of Medicine, 268:~. 965,
May 2, 1963.

Strauss, Maurice B., and Louis G. Welt, Diseases of the Kidney, Boston:
Little, Brown, and Company, 1963.

U. S. Public Health Service, U. S. Department of Health, Education,
and Welfare, Vital Statistics of the United States Mortality 1964,
Washingion, D.C.: U. S. Government Printing Office, 1966.


Chapter 3

G4

Current'Kidney Disease Control Programs

I.  INTRODUCTION

  This chapter is devoted to a brief description of current kidney
disease "program" activities and deficiencies.  "Program" as used herein

refers to an organized effort directed toward the eradication or allevia-

tion of kidney disease problems.  Kidney disease program efforts may have

an active nature, such as a research project in kidney disease, or passive

nature such as a hospital renal clinic.

  Kidney disease program efforts in this chapter are viewed from the

standpoint of program source and by program objective.  Program source is

considered in terms of federal and nonfederal.  The latter includes state

and local government, individual, philanthropic, and nongovernment

institutional financial expenditures for or on behalf of kidney disease.

  Kidney disease programs objectives may be separated into the following

functional areas:

1)




2)



3)




4)







5)

Research--Includes laboratory and clinical investigations and

developmental research efforts.

Other Methodological Studies in Kidnev Disease--Includes operational

studies, screening and detection programs, and demonstration projects.

Treatment-- Includes hospital, nursing home, physician and other

professional services for diagnosis and therapy of kidney diseases.

Facilitiesi- Includes aid in construction, remodeling or expansion

of facilities for activities in kidney disease treatment, research,

and training.

Education and Training--Includes basic education (fellowships),


specialized on-the-job training (training grants), and postgraduate

education in kidney diseases.

  The ability to describe many federal and particularly nonfederal

kidney disease program efforts in terms of expenditures is highly variable

because of insufficient or inadequate data.  In many instances kidney

disease program efforts are merged with others thereby making it difficult

to proportion accurately kidney-related expenditures among general programs.

In some instances it was necessary to use data for the year 1964 because of

its completeness and availability.  Whenever possible, programs for more

recent years are used in order to make this document action-oriented for

imminent budgetary periods,  and to take into consideration increased efforts


in this disease area.

II.   SPECIFIC FEDERAL KIDNEY DISEASE PROGRAM EFFORTS

   A number of federal agencies are currently active in kidney disease.

Some have primary responsibilities in providing patient care and others are

interested in basic and developmental research.  As in most other diseases,

there is no single federal agency charged with the responsibility for

kidney disease programs.  PHS recently indicated that there is no compre-

hensive plan for coordinated attacks against kidney disease because:

   1) Kidney disease is notoriously difficult to pinpoint as a cause for

     morbidity and mortality in the population;

   2) The variation in opinion within the medical community as to the

     desirability of large-scale dialysis and transplantation efforts;

   3) The need for more time to improve and develop research; and

   4) No single agency or organization has taken on itself the


leadership in bringing together all interested groups in kidney disease.

kidney disease program activities of specific Federal Agencies follow.



A.  u. S. Department of Health Education and Welfare (HEW)

HEW has undertaken major responsibility of kidney disease control programs

in the U. S=  Its activities range from laboratory and'clinical research
Performed or supported by the National Institutes of Health (NIH) to support
sf dialysis center demonstration projects by the Kidney Disease Control Program

cf the National Center for Chronic Disease Control.  Specific groups and

,ctivities follow.

1.  National Institutes of Health (NIH)

a.  National Institute of Arthritis and Metabolic Diseases (NIAMD)

NIAMD's primary efforts are in the area of laboratory and clinical

research and in urology and kidney diseases in general, and research

and development in chronic uremia, hemodialysis and artificial kidney

development.

  The NIAMD has traditionally.invested major funds in extramural

support of laboratory and clinical research in kidney diseases and

urologic disorders.  It was a group of Institute grantees that

developed the permanently indwelling polymer shunts which made chronic

intermittent hemodialysis possible.  The emergence of this new treat-

ment modality encouraged the Congress, in the summer of 1965, to

appropriate funds to this Institute for the pursuit of a centrally
directed program of research and development in chronic uremia, hemo-
dialysis and artificial kidney development, utilizing predominantly a
direct contract approach as well as increased research grant support.

A thorough study of the state of the art made it apparent that no

single specific direction should be followed which would exclude

others which might be relevant.  Several different types of


artificial kidneys are in use at the moment, and different

methodologies are being advocated by the various workers in

the field.  Therefore,  at this time, a variety of approaches

in artificial kidney development are being supported.   Once it

becomes evident that one or more approaches show greater

promise, efforts will be concentrated in these directions.

   The Artificial Kidney-Chronic Uremia Program was mounted

with the placement of carefully selected research and develop-

ment contracts with universities, nonprofit research laboratories

and industrial concerns which possessed relevant talents and

facilities.  These projects involve development of improved

blood cannulas; evaluation and development of new polymer surfaces

for artificial kidneys;  cannulas and membranes which do not

induce blood coagulation; design of more efficient, compact,

and less costly dialyzer systems; development of a new concept

of artificial kidney dialysis ("hollow fiber" or "capillary"

kidneys); research on and development of absorption cartridges

for blood purification;  research on the utilization of ultra-

sonics to speed up dialysis in artificial kidneys; development

of inexpensive disposable dialysis units; improvement and design

of new dialysis units with automated failsafe mechanisms;

design and development of a prototype for a portable artificial

kidney; evaluation of a special protein restricted diet in

the maintenance of uremic patients for whom chronic dialysis


is deemed not feasible or unobtainable; isolation from dialysates

and identificatinn of the as yet unknown compound(s) which is (are)

specifically responsible for the toxic symptomatology in uremia;

and many other projects related to improved dialysis methodology

or apparatus.

   An important new activity involves the establishment of a

long term central patient registry and medical information system

involving all patients maintained with the aid of chronic dialysis

in the United States (and, through cooperation of the European

Dialysis and Transplant Association, of similar patients in Europe).

This activity, which involves very close collaboration with the

Kidney Disease Control Program of PHS and with the Veterans

Administration, will permit a comparative evaluation of different

dialysis treatment methods and equipment based on a longitudinal

study of all patients involved,  from their selection for chronic

dialysis treatment onward.

  The portion of the program which is funded by extramural

research grants complements closely the contract program described

above, but is oriented more toward elucidation of clinical and

fundamental biological problems related to the treatment of

chronic uremia rather than toward hardware development. It

involves studies on urea metabolism in uremic patients undergoing

chronic dialysis; the effectiveness of peritoneal dialysis in

uremia patients; other novel approaches to blood purification in

chronic kidney failure such as dialysis of a surgically relocated,

isolated intestinal loop, lymph dialysis and dialysis in the home;

and the nature of the biochemical defects in advanced uremia.

A sunrnary of NIAMD kidney disease program expenditures is

presented in Table I.


Table I

NIAMD KIDNEY DISEASE PROGRAM EXPENDITURES FOR 1966

I           _I.__ _..._ ..__.,_. . ".__ . . . . ._.I. --..I - --..-------
-,

i i Program                      1966
---  _---- .._... - ,- . ..- _---. . . ..^_ - . . . . - . . . ..--..  .-__-.. ----___
                    -....---.....l_l_...,_^ ..-I- - .-.-_-- _. . . -- _
Research and Development:

Artificial Kidney and Dialysis     $3,151,000
  Kidney Transplant Research          593,000  I
i Other Renal and Urology Research     2,894,OOO  I

               Total           $6,638,000
            .I__U_---*l .__-.-,I_.,..... .----I---- I-. -.  --.. _.-

b.  National Institute of Allergy and Infectious Diseases (NIAID)

  NIAID's efforts are devoted to fundamental research and applied

research and development in kidney transplantation including typing

systems, immunosuppression and organ preservation.

Grant-supported research projects, intramural studies, and

organized developmental work in medical centers and industry have

been stepped up in recent years.

  The urgent need, and the short-term goal, of the tissue trans-

plantation immunology program is the identification of all the

tissue transplantation antigens and their classification according to

relative strength.  Experimental work has shown that there are

apparently only 6 to 10 major transplantation antigens rather than

the 15 to 30 which had been predicted on the basis of animal studies.

Certain immunosuppressive drugs for use in the prevention or

control of the rejection phenomenon are being studied.  Studies

are being conducted to find more effective and less toxic drugs to

control the immune response.

Two groups of investigators have produced specific immunologic


tolerance to grafts in mice and in dogs by administration of anti-

lymphocyte serum before the transplant operation. This procedure

resulted in striking prolongation of the graft and apparently

induced tolerance also to second grafts.  Another group found that

antiserum to thymus prolonged skin graft survival in rats twice

as long as antiserum to lymphocytes.

  In addition to antilymphocyte serum, total and sub-total body

irradiation, cytotoxic drugs, and surgical alterations of the lympha-

tic system have been used in attempts to reduce or eliminate the

lymphocyte population and thus increase tolerance to homografts.

These methods, however, also cause undesirable general effects, such

as depression of bone marrow and red blood cell formation.

  Paralleling the efforts to develop reagents, tests, and techniques

for applying the knowledge already gained are research projects

aimed at understanding the basic immunologic processes of the human

body.  Intramural projects in Bethesda on immunology focus on such

areas as hypersensitivity, mechanisms of the immune response,

immunochemistry of serum antibodies and antisera, and induction of

delayed hypersensitivity.  Many of these studies are closely related

to the problems of transplantation.  Fifty-nine research grants and

fifteen collaborative research contracts were supported in 1966. A

summary of NIAID kidney disease program expenditures for 1966 is

presented in Table II.


Table II

NIAID KIDNEY DISEASE PROGRAM EXPENDITURES FOR 1966

,I      -`----I

  Program                         1966 Expenditures
- ___,,__- ._-_.  _ __._~ _.--. .,___I ..__ __- ---.---I----.--.-. ~_. ._,^.
                                  _ __. - -P-,-I- --__-
                                                               ---I,-.- -7
  Intramural Research in Transplantation
   Immunology                  $ 190,000

  Research Grants-- Transplantation Immunology       3,100,000

  Collaborative Research Contracts--
   Transplantation. and Immunology                849,000

                        Total  1
                                  $4,139,000

I                                                                  _..      -.  I

C.  National Heart Institute (NHI)

Through the years, the National Heart Institute has supported

a wide variety of basic and applied research in kidney diseases

and hypertension.  One hundred and thirty research grants were

awarded in the area of renal diseases, including somewhat less than

10% in studies on fluids and electrolytes, totaling about 5.0

million dollars, or 6.0% of Heart Institute research grant funds

for FY 66.  Another 130 projects dealt predominantly with hyper-

tension, totaling 3.6 million dollars, or 4.3% of funds, and 83

grants for 3.0 million dollars representing 3.6% of research grant

funds, devoted to studies combining renal and hypertension interests.

While these reflect primarily numbers and costs of research grants,

it may be noted that approximately another 10% of these figures

were expended to support training grants and fellowships in the

same areas of research.

In FY 66, 53 of these 343 research grants were in the areas of


artificial kidney and kidney transplantation.  This includes a

significant number of projects where relatively minor commitments

are in the categories noted.

While the National Heart Institute conducts no organized

programs in kidney disease,  certain coordinated efforts can be


mentioned.  These take two forms of multi-disciplinary approach:

1) Intra-institutional, inter-departmental program projects;

     and

2) Inter-institutional cooperative studies.

Of the 226 research grants in the etiology of kidney diseases,

two are program projects dealing with renal diseases, and two other

combine attacks on renal disease and hypertension.  Support to these

four projects amounted to $838,000 in FY 66, averaging about

$210,000 per project.  Two more program projects were supported in

the renal area, directing their efforts to therapeutic implications,

and costing $905,000 or about $450,000 per project.  It may be noted

also that both these latter projects deal with kidney transplantation.

Cooperative studies represent another coordinated type of attack

on disease problems.  The Heart Institute in FY 66 supported 36

projects in three separate cooperative studies, the total cost of

which in that year was $1,374,000.  All three of these cooperative

studies emphasized clinical testing of surgical or drug therapeutic


measures, although not without inclusion also of a significant stress

on diagnostic techniques particularly in the extensive 20-project

Cooperative Study on Renovascular Hypertension.   It is of interest

that the two other studies, one on drug therapies and hypertension,

and the other dealing with antibiotic therapy of pyelonephritis in


relation to hypertension, both are conducted entirely in PHS

hospitals.  A good deal of the higher cost per project in the

Renovascular Hypertension Study reflects costs of hospitalization

and other patient care, which are not carried by the grants to

the PHS hospitals.

   All together, these coordinated efforts supported by the

Heart Institute amount to 42 projects, or 12% of those in the

total area of kidney and hypertension research, with a support

level of slightly over $3,000,000 (see Table III), or about a

quarter of the total research grant budget for these areas.  Thus,

while the Institute continues to emphasize support of individual,

unstructured, non-directed research on hypertension and kidney

disease, these more coordinated program projects and cooperative

studies represent significant portions of Heart Institute support

to these fields, stressing particularly many aspects of therapeutic



measures.

Table III

NHI RESEARCH EXPENDITURES ON KIDNEY DISEASE

  Program                   1966 Expenditures
                 -------VI_ _I__-_-_- .._ -____


  Renal Disease and Hypertension      $1,743,000

  Cooperative Studies               1,374,ooo
I                  Total          $3,117,000

I                __-_-__--__.- .._.. ~- .-.- .~.                            -.I


d.  Division of Research Facilities and Resources (DRFR)

  Several programs are administered by DRFR which include

support of research in kidney diseases.

  In FY 1966, the General Clinical Research Centers program

provided an estimated $4.5 million for kidney disease research

not including research in hypertension and diabetes.   This

program provides for the cost of remodeling and renovation

necessary to establish the resource and for operating costs such

as hospitalization, research nursing care and support of specialized

technical personnel.  Laboratory support in these centers is limited

to procedures required by several different investigators.   The

research conducted in these centers is controlled through competi-

tion adjudicated by a local advisory committee.  Since many of the

investigators utilize the resource simultaneously, the award pro-

vides a flexible mechanism of bed-support which can readily adapt

to the needs of many investigators at any particular time.

  The Division has two other programs on which kidney research

depends indirectly.  The Health Research Facilities Program, budgeted

at $50 million, provides matching funds for the construction of

research facilities.  Any future research programs in renal diseases

requiring additional space may depend heavily on this program.

  A second program is the General Research Support Program,

currently budgeted at $61 million.  This program assists institutions

heavily involved in sponsored biomedical research to maintain a

degree of flexibility in furthering their own biomedical research

and research training goals.  Thus this program provides backup


support for many of the categorical grants from the institutes.

A summary of pertinent Division of Research Facilities and

Resources expenditures is presented in Table IV.





                      Table IV

  ESTIMATED DRFR DIRECT KIDNEY DISEASE PROGRAM EXPENDITURES





---.---          ..uL------
  Program                    1966 Expenditures
                                                 --m-e- ..-- ---__..-_-
                                 ---m..- .u_ -7
                                                         I_---


   General Clinical Research Centers:
        Kidney Disease             $4,500,000



                                -----.__._. -. .-.. _.._ .-....   _ _ _   -__-I


2.  Kidney Disease Control Branch, National Center for Chronic Disease


   Control

  The Kidney Disease Control Program of the National Center for

Chronic Disease Control has responsibilities in all areas relating

to the development and demonstration of the dialysis method in commu-

nities, the training of professional and technical personnel in

dialysis therapy, public and professional information and education

activities, and appropriate related data collection and analysis.   The

Branch serves as the Public Health Service's consultative unit in

dealing with official and other health agencies, hospitals, and

practitioners in all aspects of the provision of dialysis services.

In addition to these dialysis-related activities, the Kidney Disease

Control Program conducts a broad range of preventive and educational

activities in the broad kidney disease field.

  Specific responsibilities in the dialysis-related areas follow.



a.  Development and Demonstration Activities

  Utilizing the grant authority of Section 316 of the Public

Health Services Act, the Kidney Disease Control Program actively

promotes the development of community dialysis demonstration

programs in various areas of the country.  In addition to demon-

strating the feasibility of the treatment in the community setting,

these programs allow exploration of methods of financing dialysis


programs, provide expanded training opportunities, and allow

testing of new patterns in the provision of dialysis services. A

total of 15 community dialysis programs are presently being funded.

b.  Training Activities

  In addition to providing training opportunities through the

grant program, the Branch is responsible for development of train-

ing materials and techniques for use in both community centers and

home dialysis programs.  This extends to all types of professional

and technical personnel and complements the limited direct assist-

ance for training in centers receiving grants.

C.

and

Public and Professional Information and Education

In this area, the Branch is responsible for the development

distribution of both technical and non-technical materials

related to the dialysis method, and for the provision of accurate

information on all aspects of the problem to the public through

the various media.


d.  Data Collection and Analysis

  The Branch engages in a continuing data collection and analysis

function directed towards the acquisition of quantitative information


   from dialysis programs--regardless of the mode of support--and

   analysis of the information in order to gain an accurate assess-

   ment of the current status of the method.  The data is disseminated

   to interested parties inside and outside government, and is

   utilized in the long-range planning functions of the Branch.

  A summary of the Kidney Disease Control Branch Program's expenditures

are presented in Table V.

Table V

SUMMARY OF KIDNEY DISEASE CONTROL BRANCH PROGRAM EXPENDITURES IN 1966

1
1 Community Dialysis
I

  Prevention
!
Basic Data Development

Information and Training Mater ia IS

/                 Total

         -. -__   _

3.  Bureau of Health Services

Present program activities of the Bureau of

_ .._ -_.. ___^._ ----I

1966 Expenditures 1
_ .- ._  _       '-   .-. ..,. ._-___
_  . ,. : 1

$2,617,000 ;

385,000        I
              3

156,000 :

  249,000

$3,407,000

             -.u

Health Services related

to kidney problems include basic and clinical research programs which

are being conducted at four Public Health Service general hospitals.

These programs encompass investigations in normal renal physiology as

well as a broad range of primary and secondary renal abnormalities. A

cooperative study involving seven general hospitals is attempting to


define the pathogenesis and natural history of chronic pyelonephritis
and to assess the response to long-term suppressive antibiotic therapy.
One of the hospitals has established a kidney disease screening clinic
to evaluate patients with suspected renal abnormalities.  A second

cooperative study of hypertension includes the renal causes and com-

plications of this entity.  Both cooperative studies are funded by the NHI.

With regard to training in this subspecialty, it has been necessary

until recently to provide training outside-the-service in order to

develop career investigators for the Bureau and the Service.  Individuals,

who received this training, now provide the competence for the present

research programs and for future training programs.
Expenditures by the Bureau of Health Services for research and train-

ing for 1966 are presented in Table VI.

Table VI

BUREAU OF HEALTH SERVICES KIDNEY DISEASE RESEARCH AND
       TRAINING EXPENDITURES FOR 1966

-.---lll__ .._ __.. .
1                           . . ,^...- - ^ mm -"I--F

  Program             1966 Expenditures
           ~--_.----asl-l-w -1_
Lwr"..----                   --*-w.--e..-*41n
                    ..-    . . . -. - -- _-_..- I.-_^-__

i
  Training

f   Research


             Total

I- --. . ._. .-.

4.  Vocational Rehabilitation Administration

At present the magnitude of specifically identified support for the

Vocational Rehabilitation Administration for patients with kidney disease

is not readily ascertainable.


B.  The Veteran's Administration

  The Veteran's Administration is charged with the responsibility of pro-

viding medical care, and to conduct medical research, designed to maintain

or improve the health of its beneficiaries.  Within this broad mandate the

Veteran's Administration has exerted a significant effort in the kidney

disease area.

  The large majority of Veteran's Administration funds directed towards

kidney diseases is expended in the area of clinical care. Information as to

the level of effort in.this area is scanty,  and overall costs are not avail-


able.  However, discharge diagnoses from the Veteran's Administration hospitals

can provide clues on the size of the problem.  In calendar years 1962-64,

patients discharged from Veteran's Administration hospitals with selected

principal and associated renal diagnoses averaged nearly 50,000 per year.

The number of deaths with kidney disease as a principal diagnosis has.remained

relatively constant at roughly 1,600 per year although the distribution of

diagnoses has changed somewhat.

  A little over three years ago the Veteran's Administration decided to

include a chronic hemodialysis capability within its hospital system.,

Since that time, 13 hospital units have been established. Actual cost

analysis of this program is very difficult since a large share of the cost

of the activity is supported from basic hospital budgets and is not sepa-

rately identifiable.  Specific allocations by the Veteran's Administration

Central Office for unit activation over and above these basic hospital costs

has been estLmated at $2,476,000.

  At the present time, the Veteran's Administration estimates that approxi-

mately 175 patients are being maintained on chronic intermittent hemodialysis.

It further estimates  that the future development of units already established


,&d enable it to perhaps double this caseload. Analysis of the mortality
data mentioned earli er has led the Veteran's Administration to estimate that

roughly 200 to 600 of the 1,600 individuals dying each year due to kidney
disease would be suitable candidates for chronic hemdiaipis programs.

Kidney transplant efforts are being conducted within the hospital

System of the Veteran's Administration and generally are associated with

a chronic hemodialysis program.  Reliable data on veterans treated with

kidney transplantation, however, are not available.  At a recent meeting,

surgeons from most of the Veteran's Administration hospitals estimated

that approximately 100 such operations were reported as having been

performed during the past three years.  However, a considerable number of

veterans have been referred to non-Federal institutions for transplants.

  Research efforts sponsored directly by the Veterans Administration

constitute only a very modest part of the overall national investment
in kidney research.  Research projects are underway in transplantation

and dialysis as well as in other kidney research areas.

A summary of estimated expenditures for VA kidney disease research

programs in 1966 is presented in Table VII.

Table VII

ESTIMATED VA EXPENDITURES FOR KIDNEY DISEASE RESEARCH PROGRAMS IN 1966

   --

Program

P-v-----

              1966 Expenditures
                           -.-T-s
    -

Research
(dialysis and transplantation)       $ 734,000

I_- _.                          ..-- ..-- we_... --_ _.-_.


C.  Other Federal Agencies

  Program efforts by other Federal agencies include those of research by

the Department of Defense, Atomic Energy Commission, U. S. Department of

Agriculture, National Aeronautics Space Administration, and National

Science Foundation.

  With the exception of the Department of Defense, expenditures by other

Federal agencies in kidney disease are for research and are summarized in

Table VIII.  Expenditures by the Department of Defense for treatment of kidney

disease have not been included.

Table VIII

KIDNEY DISEASE RESEARCH PROGRAM EXPENDITURES BY
      OTHER FEDERAL AGENCIES IN 1966

       -m-m-..._. .- .p--..----PI-

Agency               1966 Expenditures
                                     .__-.,.---,--
                           .-.--I                -



  DOD                    $ 440,000


  AEC                       65,000


  USDA                     105,276

/ NASA                      85,400

I
/
/   NSF                       22,034

Other Nonspecified

        Total

  617,290

$1,335,000
     i

L           -I.-- -.  -- __.._                       _. .^. .-I


III..  NONFEDERAL EXPENDITURES FOR KIDNEY DISEASE PROGRAMS

There are numerous state and local programs which expend money for

various types of kidney disease programs including construction of facilities,

treatment and prevention.  These have not been included in this report.

Certain nonfederal agencies carry on.active research, education, and

general service programs in kidney disease.  A description of some of these

follows.

A.  The American Heart Association

In general,  the aims of the American Heart Association are to combat

diseases of the heart and circulation and to provide positive benefits

for the health of the people of the United States.  Because of the asso-

ciation of renal diseases to those of the circulation, the American Heart

Association's program activities include a substantial effort directed

toward the control of renal diseases.  Although the Heart Association has

traditionally placed its primary emphasis on the support of the acquisition

of new knowledge through research, it also has embarked on broad programs

of public and professional education and has supported specific community

programs designed to contribute to the understanding and prevention of

cardiovascular diseases as well as to provide support for the individual

patient with cardiovascular disease.  In the renal disease area, the largest

portion of effort has been expended in the areas of research with particular

emphasis on the relationship between hypertension and kidney disease. It

is anticipated that future efforts to be expended in this area will remain

at approximately the present level and the Heart Association does not plan

to extend its efforts in renal disease into areas of other than research.

Table IX shows the 1966 level of effort in renal and directly related research.


Table IX

AMERICAN HEART ASSOCIATION EXPENDITURES IN RENAL RESEARCH FOR 1966

Program

1966 Expenditures
        -e--.-e..."

National


Local

Total

$ 618,000



$1,060,000


I-- --me-".

B.  National Kidney Foundation

  The aim of the National Kidney Foundation is to improve the care and

treatment of those afflicted with kidney disease through the support of

research into the incidence, causes, treatment, prevention, and cure of

kidney diseases.  The foundation also aims to promote professional and public

education directed toward improving care and treatment of those afflicted with

kidney disease.  Through its lay and scientific advisory groups, the

National Kidney Foundation cooperates with other agencies, public and private,


to achieve these aims.  Over the last five years the National Kidney Foundation
has engaged in several broad areas of activity. Patient care services have `

included the distribution of drugs and medication, at cost or gratis,

through its Drug Bank Program.  A number of renal clinics has been promoted

and assisted throughout the United States.  Direct support of research

activities has consumed the major portion of its resources, although a

substantial effort also has been directed toward public and professional


education.  Table X shows the 1966 level of expenditures by the National

Kidney Foundation for renal research, services, and education.


34

Table X

NATIONAL KIDNEY FOUNDATION EXPENDITURES FOR 1966

Program

    1966 Expenditures
__I. -,---m

Research


Services


Education

Total

$350,000

200,000

200,000

$750,000

C.  John Hartford Foundation

The John Hartford Foundation expended money for renal disease primarily
in the area of research on dialysis and urinary disease problems.  Expendi-

tures for 1964 totaledabout$796,000.


Chapter 4

Research Methodology

I.   INTRODUCTION

  This chapter presents the methodology used in the analysis of projected

kidney disease programs.  This methodology is designed to identify significant

kidney diseases in the United States, to postulate programs designed to

alleviate the effects of these diseases,  and to estimate the benefits and

costs associated with such programs.  A schematic of this methodology is

presented in Figure 1.

II.   DISEASES STUDIED

  Because of the complex diffuse etiologies and the large variety of

diseases that affect the kidney, it was imperative that the disease spectrum

be narrowed in order to identify meaningful categories of kidney disease

which will serve as foci for important research and control programs (please

see Chapter 2).  Prominent kidney diseases were identified and grouped in

the following manner:*

1) Infectious Diseases of the Urinary Tract


       Disease

  Infections of the kidney

  Cystitis

  Urathritis (non-venereal)

  Pyelitis and pyelonephritis of pregnancy

ICD Code


600


605


607


640

*

IC&' codes and nomenclatures were used to identify diseases of interest
as most available statistics on mortality and morbidity follow these
classifications.


    v ~. ..--       I
'Identify Important,
Diseases           .I
        1
        I

Infectious Diseases of the Urinary Tract

,Group Important
I Diseases

Kidney Diseases Related to Hypersensitivity
   Phenomena
Kidney Diseases Related to Hypertensive

*- -    --.._ ^_._. ,
        ,                     Vascular Diseases
        /
    I              End-Stage Kidney Disease

*
1.  Program with current HEW funding level
   and current state of the

. .--L

Derive Basic
Kidney Disease
Programs for
Disease Groups

--_.--... .~.
1   - .-.i

Estimate Costs j
of Programs for
Disease Groups

Summarize

   art.
2.  Program with intermediate HEW funding
  level and current state of the
    art.
3.  Program with accelerated HEW funding
  level and current state of
   the art.
4.  Program with accelerated HEW funding
  level for 1975 and advanced state of
   the art.

Program cost derived from published data
and from "best estimates."

Benefits of programs under current state
  of the art derived from published
  studies and expert opinions.
Benefits of programs under advanced state
   of the art derived from "best
   estimates."

L

Fig. 1.  Methodology Schematic.

85a


2) Kidney Diseases Related to Hypersensitivity
   Phenomena

Disease

Acute nephritis

Nephritis with edema, including nephrosis

Chronic nephritis

Nephritis not specified as acute or chronic

Other renal sclerosis

3) Kidney Diseases Related to Hypertensive Vascular
   Diseases

Disease

Essential benign hypertensive heart disease

Essential malignant hypertensive heart disease

Hypertensive heart disease with arteriolar
nephrosclerosis

Other and unspecified hypertensive heart disease

Essential benign hypertension

Essential malignant hypertension

Hypertension with arteriolar nephrosclerosis

Other hypertensive disease without mention
of heart

ICD Code


  590


  591


  592


  593

  594

ICD Code


  440


  441

442

443

444


445


446

447

4) End-Stage Kidney Disease

Although end-stage kidney disease is the eventual result of

advanced or untreated primary renal disease, it is considered

separately because of the unique treatments which can be employed;

I.e., chronic intermittent dialysis and kidney transplantation.

5) Other Diseases Affecting the Kidney

A variety of other diseases falls within this category.   Some


87

(i.e., neoplasm6 of the kidney) fall within other disease control


programs.  These diseases have not been considered in the detailed

analysis for reasons stated in Chapter I, E, 1 & 2, but many

should be considered in a more comprehensive study.

III.  KIDNEY DISEASE PROGRAMS STUDIED

  A limited number of hypothetical kidney disease programs were studied.
These programs are delineated by time, state of the art, and funding level.
The time periods used included fiscal year 1966 (a year for which reasonably

complete costing data are available) and 1975 (a year for which significant
advances in the state of the art are anticipated). Both current and

advanced states of the art are considered in this analysis; the current state

of the art refers to 1966 modus operandi in the control of kidney disease.

The advanced state is that which would exist following significant research

advances in kidney disease.  Program funding levels were considered from the

standpoint of HEW participation (third party payments and general direct

health expenditures were not considered) and include the current level of

expenditures (1966), an intermediate level of spending, and an accelerated

expenditure level.  The hypothetical intermediate funding level is two to

three times greater than the current level and is used to analyze various

programming possibilities at a more accelerated level.  The hypothetical

accelerated funding level is even greater than the intermediate level (about
six times greater than the current level). Using these parameters, four

major programs were developed under which each disease group is studied.

These are:


1) Program A

     This program describes the distribution of the total funds

  available from HEW (currently approximately $47,000,000) and other

  kidney disease programs for fiscal year 1966 for which benefits

  are maximized within the current state of the art for 1966.

2) Program B

     This program describes an intermediate HEW funding level

  (two to three times greater than the amount available for fiscal

  year 1966) for which benefits are maximized within the current

   state of the art for 1966.

3) Program C

     This program presents an "accelerated" HEW funding level

  (about six times greater than fiscal year 1966) for which benefits

   are maximized within the current state of the art for 1966.

4) Program D

     This program describes an accelerated HEW funding level (as

  in Program C) for which benefits are maximized within an advanced

   state of the art for 1975.  The advanced state of the art as used

  here implies that significant advances in research have been made

  and that the control of renal disease is operational.

In general, the effects of the various programs projected are mutually

exclusive.  First, the programs proposed for any given year do not affect

the programs proposed for any other year; this assumption is necessary in

order to estimate fully the benefits and costs of a single program.  Secondly,

the programs proposed for a given disease group are not assumed to affect

the programs for other disease groupings.  Again,  this is done to estimate


&sely the effects of a single program.  Moreover, within the imposed

time period (1966 to 1975) it is felt that important inter-effects would

not have occurred; this is especially true when considering the preventive

program components and their effects on end-stage kidney disease.

In addition, the programs are in a steady state, that is, the full

effect of the programs is assumed to have been attained within the year

under consideration.  It is assumed that personnel build-up, initial costs,


etc., which are inevitable in establishing a program, have already been

arranged.

IV.   COSTS OF KIDNEY DISEASE PROGRAMS

The costs associated with the various kidney disease programs were

arrived at by utilizing various sources and assuming a constant 1966 dollar

value throughout.             21
         PHS publications- and a current study at the Research
Triangle Institutr' provided basic cost data.  Unpublished data from the
National Center for Health Statistics,A' the National Drug and Therapeutic
Index,5'                          61
      the Professional Activities Service,- and published data from

the American Hospital Associatio? provided information on the costs

associated with morbidity and mortality relating to kidney diseases.  "Cc's t

to HEW" refers only to the direct health expenditures of HEW (excluding

third party payments) generated by the programs described.  "Total cost"

refers to all expenditures anticipated for the programs described.

  While the costs of certain specific treatments such as dialysis are

available (although subject to range errors), other costs such as that

of implementing kidney disease prevention programs, including mass screening,


                              xl

were not generally available.  Accordingly, it was necessary to make "best

estimates" based upon informed medical judgment. As such, these figures

represent a first approximation of the desired data.  Implicit in such

methodology is that as more data becomes available, these estimates can be

refined.

   When screening and educational programs are described in the text, the

assumption is always made that the particular program component studied is

part of a general screening and educational program.

V.  BENEFITS OF KIDNEY DISEASE PROGRAMS

  Benefits derived from proposed kidney disease programs are measured only

in terms of the impact upon mortality, prevalence, and morbid days in select

population groups, i.e., number of lives saved, number of cases reduced, and

number of morbid days prevented.  Reduced mortality, reduced prevalence, and

reduced morbid days (defined as days of restricted activity), are benefits

measured in disease groups 1, 2 and 3 above.  Reduced mortality only was used

for disease group 4 above.  No attempt was made to estimate the benefits

derived from a reduction of indirect costs.  In addition, no attempts

were made to estimate the returns made to the general economy by an individua:

whose life has been saved or lengthened or where disease has been terminated.

In the case of the disease groups related to infection, hypersensitivity,

and hypertension, a select or high-risk population group was identified and

data were collected on current mortality, prevalence, and morbidity. Estimate

were then made on the effect of a projected program on morbidity and mortality

for these groups.  The difference between current mortality and morbidity

per year and those estimated to be the effect of the proposed program


91

(assuming the program has become fully established) comprise the short-term

benefits discussed in this analysis.  Long-term benefits for these groups
cnot accounting for changes in these groups over the years) were estimated
in terms of reduction in the number of cases of end-stage kidney disease,
joth on an annual and on a cumulative basis.

Annual long-term benefits assume that a sufficient length of time has

elapsed after the implementation of the programs to decrease maximally the yearly

number of cases of end-stage kidney disease which would eventually have

occurred in the high-risk groups without such a program.

Cumulative long-term benefits refer to the summary effect on the number

of cases of end-stage kidney disease which would have occurred without the

projected program.  Each program is analyzed for a surveyed population and
does not take into account changes in that population over the years.

For the end-stage kidney disease group, the treated population was

identified and estimates made as to the number of deaths prevented as a

result of the program in a particular year.  No attempt was made to measure

short-term benefits in terms of reduced morbid days.  Because of the relatively

high incidence of death in these groups, the uncritical estimation of morbid

days can be very misleading.  For example, it can be shown in some cases
that a patient in kidney failure may have fewer morbid days if he succumbs
to his disease after conservative treatment only, rather than if his life

were prolonged with the aid of chronic dialysis.

VI.  METHODOLOGY LIMITATIONS

Because of the time limits involved, this study has several limitations.

bong these are:


1)

2)

3)

4)

5)

6)

7)

8)

9)

10)






11)

A limited number of kidney disease control programs were considered;

A limited number of diseases were analyzed;

Diseases were grouped rather than studied singly;

Benefit measures employed did not include reduction in indirect costs;

Only two time periods, 10 years apart, were studied;

Only 4 funding levels were considered;

Only high-risk population groups were considered;

Cohort analysis was not used in estimating benefits.   In future

studies the benefits attributed to various programs could be followed

in a cohort of some fixed size from birth to death;

Inflationary trends were not taken into account;

Associated benefits such as the simultaneous effect on rheumatic

heart disease of a program to control acute glomerulonephritis were

pointed out but not measured; and

The effect of possible changes in the general standard of living was

not taken into account.

   All of the above limitations should be examined in any continuation of this

study.  Despite these limitations, however, the results of this study are

significant insofar as it provides some idea of the dimension of the problem

and a rather specific indication of benefits to be derived from alternative

programs and funding levels.


93

FOOTNOTES

Seventh Revision Conference, Ninth World Health Assembly, Manual of the
International Classification of Diseases, Geneva:  World Health Organization,
1957.

Various monographs from the National Center for Health Statistics,
Vital and Health Statistics, series.

Albert V. Alhadeff, Benjamin S. H. Harris, III, and Jerome B. Hallan,
"Preliminary Estimates of the Direct Costs of Kidney Disease and Selected
Diseases of the Urinary System," Research Memorandum OU-281A-1, Research
Triangle Park, N. C.:  Research Triangle Institute, April 1967.

National Center for Health Statistics, Unpublished Data on U.S.
Mortality and Morbidity, U.S. Public Health Service, Washington, 1967.

National Drug and Therapeutic Index, Inc., Unpublished Data on Drug Costs
and Physician Visits, Ambler, Pa., (1967).

Professional Activities Services, Inc., Unpublished Data on Short Stay
Hospital Patients, Ann Arbor, Michigan, 1967.

"Guide Issue", Hospitals.  Part 2, Vol. 39, No. 15, American Hospital
Association: August 1, 1965.


94

Chapter 5

Program Analysis

I.   INTRODUCTION

  This chapter discusses in detail the programs designed for the four

disease groups under consideration in this study. As mentioned earlier,

the disease groups include infectious diseases of the kidney and urinary

tract, hypersensitivity diseases of the kidney, kidney disease related to

hypertensive vascular diseases, and end-stage kidney disease.  These disease

groups are studied within the constraints of four hypothetical programs

varying in budgetary level, state of the art, and time.  Three hypothetical

programs for fiscal year 1966 have been postulated based on a low (reflecting

current HEW expenditures of about $47,000,000), intermediate (with
$117,800,000 HEW support), and high (with $290,000,000 HEW support) expendi-

ture level.  In addition to these three programs, a fourth program reflecting

advances in the state of the art on an accelerated ($293,000,000 HEW support)

level which could be operational by 1975, is considered. Possible activities

for each disease group are projected within the framework of each of the

four programs mentioned above.  In each case attempts have been made realistic-

ally to evaluate what will happen within the constraints of the program and

the disease under consideration.

  As each disease group was being studied within the program constraints,

realistic program components were postulated including their costs and


estimated benefits.  The following components were used:

   1) Prevention, Diagnosis, and Treatment


95

This component refers to the screening, confirmatory diagnostic

tests, relevant' treatment follow-up, and related general educational

and administrative steps needed to ameliorate or control the

disease.  (This includes postgraduate physician education and relevant

lay education).

2) Research

  Research includes problem-focussed laboratory and clinical

studies as well as fundamental, individually oriented research

supported by grants.

3) Training

  The training of researcher workers and other specialized medical
personnel other than the general educational efforts referred to in

the first program component is of concern here.

4) Facilities

Included here is the real estate and hard core equipment that

support any disease control program.

  Both short and long-term benefits were estimated.   Short-term benefits

were determined in terms of reduction per year in mortality, prevalence and

morbid days.  Long-term benefits were determined on the basis of an annual

reduction in end-stage uremia, and on a cumulative (life-long) basis for the

high-risk population being considered by the specific program.

   As indicated in the methodology, in many instances it was necessary to

use "best estimatesll based on informed medical judgment. These estimates are

obviously subject to range errors, but are representative, by and large, of

the facts that can be drawn from current information.


  The remainder of this chapter is divided into major sections, according

to the various disease groups.  Within each of these sections the four

hypothetical programs are considered.

   Benefit-cost tables summarize the analysis of each hypothetical program.

   The reader of this chapter is referred to Chapter 1 of the report

(Introduction and Overall Summary) for a textual summary of the various

analyses and for a discussion of the findings within the overall framework

of the kidney disease problem.


97

II.  INFECTIOUS DISEASES 0~ THE URINARY TRACT

.A.  Introduction

This section pertains to programs needed for the control of infectious

diseases of the urinary tract.

In 1966, 10,550 death&' were estimated to have had infectious disease

L7f the urinary tract as the underlying cause of death.  In 1966, there were

an estimated 1,963,OOO cases of known infections of the urinary tract and an

associated 38,197,OOO days of restricted activity, 17,277,OOO days of bed

disability,                     21
      and 4,185,OOO work-loss days.-  The actual prevalence of the
                                              3/
disease is at least 3 to 4.times higher (i.e., 6,000,OOO to 8,000,000).-
The discrepancy is due to the presence of numerous asymptomatic and unreported

cases.

The statistics and estimates used and described in the text are based,

in most cases, on information gathered from the literature.  In many instances

the validity of such data, upon which proj'ections are based, might be

questionable.  However, the information is often quite reliable and has been

used realistically to project the findings onto overall population figures.
Four programs have been considered in this analysis (see Chapter 4,

Research Methodology).  The following sections describe these in detail.


B.  Infectious Diseases of the Urinary Tract, Hypothetical Program at Current
  HEW Expenditure Level, Based on Current State of the Art

  1.  Introduction

    This program has four components:

    1) Screening, diagnosis, treatment, and supportive physician and lay

       education and administration;


98

2) Research;

3) Training; and

4) Facilities.

  As illustrated in Figure 1, the total cost for this program is estimated

to be $158,265,000.  Of this amount, HEW funds would account for $9,203,000.

A discussion of the various program components follows.

2.  Screening, Diagnosis, Treatment, and Supportive Education and
   Administration

Within the present state of the art, a program would be developed to

screen high-risk patient groups for the presence of urinary tract infections.

The highest number would probably come from:

1) Hospitalized in-patients,

2) Non-hospitalized pregnant females, and

3) Non-hospitalized diabetic patients.

These population groups are known to have a high incidence of urinary

4/

tract infections.- Furthermore, screening tests can be applied to these

groups with a minimum of organizational development, since they are usually

already under a physician's care.  The development of this program presupposes

the presence of an accurate screening test, such as a refined Greiss Test

(nitrate reduction test), which will be incorporated into a routine examina-

tion of the urine in these population groups.  The selection of these high-

risk groups has been somewhat arbitrary, and further study may indicate that

other groups such as school children and college students should also be

screened.  It was felt, however, that the groups selected would be most likely

to derive maximum benefits under this program.

a.  Relevant Population and Program Component Costs

  It is estimated that during 1966, 29,147,OOO individuals were


100









50









  9.2

Diagnosis and

HEN

Program

Diagnosis and
Treatment
  (151.1)

Research (5.3)

Total

~ Training
/      (0.5)
-Facilities (1.3)

Fig. 1.  Infectious Diseases of the Urinary Tract, Hypothetical. Program Costs
    at Current HEW Expenditure Level, Based on the Current State of the
       Art.                     98a


33

short and long-term residents in hospitals and nursing homes in the
u. s.5'  In addition, in the U.  S. it is estimated that there were
                            6/

4,497,OOO non-hospitalized pregnant females- and 2,422,OOO non-
hospitalized diabetics."  Thus, the total high risk group was comprised

of 36,066,OOO individuals.  It is also estimated that significant

bacteriuria exists in 20% of the hospitalized in-patient population,

6% of non-hospitalized pregnant females, and 15% of non-hospitalized
      8/
diabetics.-  The projected prevalence in this population is then estimated
                       9/

to be 6,462,520 cases of bacteriuria-  (about 18% of the population

at risk).

   It is also estimated that a screening program will be able to
detect 85% (5,493,140) of the patients having significant bacteriuria.lO'

Assuming a 5% false positive screening rate, 5,767,800 positive tests
will appear in this program (105% of 5,493,140).11'  Those individuals

with positive screening results will require a confirmatory urine test

(urine culture, bacterial colony count and antibiotic sensitivity test).

A second repeat procedure for the 5,493,140 confirmed cases is necessary

following therapy in order to ascertain the degree of success of treatment.

The estimated cost for the detection test as part of a general

screening program is $0.25 per person tested ($0.125 for the cost of
                                   121

the test and $0.125 for the cost of administration).-   The total cost

is calculated to be $9,017,00~ of which HEW will contribute $1,803,000

for technical and financial support.  The cost for a single confirmatory

urine culture, colony count, and sensitivity test is $7.50,&'  and the total

cost for confirmatory tests is then $84,457,000 which will be contributed

by sources other than HEW.

Treatment costs are estimated at $10.00 per patient (note that

these individuals are already under physicians' care and that most of


this cost is for drugs).  The total cost of therapy would be

$54,931,400 for the 5,493,140 individuals with confirmed infections.

This method of detection and treatment would not require individuals

who are not already hospitalized to be placed in such treatment care

facilities; therefore, additional costs for hospitalization are not

anticipated.  However, it is quite probable that an individual with

an infection of the kidney may require hospitalization.   It should

also be emphasized that this projected cost (most of which will be

borne by sources other than HEW) is a bare minimum estimate and

allows only for detection, diagnosis, and drug treatment. It does

not allow for inquiries into associated or predisposing factors of

infection, follow-up therapeutic courses, or laboratory studies ,when


needed.

   Extensive educational and administrative financial support is

anticipated from HEW.  Any screening program that is to be instituted

in hospitals throughuut the country would require a vigorous educa-

tional program concerning proper interpretation of tests, adequate

therapy, and appropriate follow-up procedures.  It is felt that the

7,000 or so hospitals in the U. S. should be exposed to an educational

program regarding the entire problem of urinary tract infections in

order to achieve maximum program effectiveness (i.e., eradication of

bacteriuria).  About $l,OOO,OOO ($140 per hospital) as part of a kidney

disease general education program will be required from HEW, and $335,000
                                              151

is expected from other sources for the education of medical personnel.-

   $l,OOO,OOO is required from HEW for administrative purposes plus
$335,000 from other sources.*' The total cost to HEW is $2,000,000,



and $670,000 is to be spent by other agencies.

b.   Short-Term Benefits

  From an estimated base of 6,800 deaths in the population screened
                                171
which would occur without this program component,-  a 1% reduction in

immediate mortality is anticipated due to the successful treatment of

acute pyelonephritis (if it is detected at an early stage before severe
                   181
tissue damage has occurred).- Therefore, a reduction in mortality of

70 deaths per year is estimated.

  In addition, there is a reduction in the prevalence of significant

bacteriuria in 3,231,260 patients (50% of 6,462,520). This 50% reduc-

tion is based on the supposition that the majority of cases detected

will be of simple bacteriuria, in the absence of tissue infection, which

responds well to treatment.  It is understood that the first course of

therapy for patients with bacteriuria in acute infections would be

highly successful, but is is not anticipated that a permanent cure

will be achieved in individuals with chronic urinary tract infections.

  With therapy, the number of morbid days could be reduced by 65%
from the base of 24,557,580 to 15,962,427.191



C.  Long-Term Benefits

  A significant benefit from this early detection program will be an

ultimate reduction in mortality due to end-stage renal disease resulting
                          19Aj
from earlier urinary tract infections.-  After a diagnosis of infec-

tion is made, further study of the patient would lead to the detection

of factors predisposing to or associated with that infection. It

should be pointed out that new methods of anti-infectious therapy could
                                            201
possibly increase the cure rate for the population-at-risk to 75%.-


(1) Annual Long-Term Benefits

At present, it is estimated that 20% (1,750) of an esti-

mated total cases (8,500) of end-stage kidney disease per year
                          211
can be averted by current medical therapy.-

(2) Cumulative Long-Term Benefits

  It is estimated that in time 5% (323,126) of the 6,462,520

individuals having significant bacteriuria may have developed a

significant urinary tract infection.  Of this 5X, approximately

40% (129,250) may eventually die in renal failure. Implementation

of the above program would be expected to reduce this mortality by
                                221

  20% (25,850) based on current methods of therapy.-

3.  Research

  Because of problems peculiar to urinary tract infection, [i.e., the

poor response to therapy (20% cure rate) and the difficulty in isolating

bacteria from end-stage kidneys resulting from infection], a great deal

of research, both laboratory and clinical, must be undertaken before a

more effective program can be administered in the prevention of urinary

tract infections.

a.  Laboratory Research

  Laboratory research should be concentrated in these areas:

  1) A relationship of viral agents to renal disease;

  2) The identification and treatment of host-factors which

    predispose the host to urinary tract infections;

  3) The role of immunologic phenomena in bacterial and/or viral

infections of the kidney;

4) The role of vascular and metabolic diseases in urinary tract

infections;


  5) The role of various chemical agents (e.g., phenacetin) in

     renal tissue infection;

  6) The nature of the exudative response to renal infection;

  7) The nature of connective tissue proliferation in renal

      tissue;

  8) A classification of the organisms causing renal infections

     and the identification of toxins, enzymes, etc., produced

     by these organisms; and

  9) The pharmacology of specific antibiotics including drug

     inhibitors affecting the viability of microorganisms in


      renal tissue.


   No sound estimate can be made for the cost of each of these

basic research programs, but approximately $1,500,000 should be
                                    231
made available in the form of research grants from HEW.-


b.   Clinical Research

  Clinical research must include studies to evaluate therapeutic

programs and long-term follow-up of patients with kidney infections,

and attempts to identify crucial points in the natural history of the

disease at which therapy is most effective.   Other studies would be

attempted with susceptible patients (pregnant females, persons

with obstructive uropathy, diabetics, etc.) to discover pertinent

facts in the pathogenesis of renal infection.   It is estimated that

each large scale clinical study will cost approximately $500,000 per
   241
year.-  This amount is based on existing cooperative studies and

does not include the cost of hospitalization or laboratory tests

which must be borne by other sources.  Four cooperative studies

will be developed, each costing $500,000: one study will address


itself to a study of the natural history of renal infection; two,

to therapeutic trials; and a fourth to the pathogenesis of the

disease in susceptible sub-groups of patients.

  An additional $500,000 will be used for detailed studies on

a small group of patients with renal infection.  This study would

encompass the definition of changes in renal function, the effects

of specific antibacterial agents on the infection, the trial of new

treatments such as chronic water loading, etc.

   Total clinical research expenditures will amount to $2,500,000

supported by HEW.

Total costs for research will be $5,330,000 of which HEW would

contribute $4,000,000; $1,330,000 would come from other sources.

4.  Training

  Training includes the financial support of research fellows engaged

in clinical laboratory studies,  and the cost of relevant facilities.

Support and laboratory facilities for approximately 12 fellows for one

year would cost HEW approximately $400,000 plus $130,000 from other
                         251
sources, yielding a total of $530,000.-

5.   Facilities

  This program utilizes only existing facilities; however, laboratory

and hospital space is limited at present and in order to develop an

efficient program as outlined, expanded facilities would undoubtedly be

required for research and for the screening of patients for urinary

tract infection.  Consequently, it is anticipated that about $l,OOO,OOO

would be expended by HEW and an additional $330,000 by other sources,

yielding a total of $1,330,000.


  A benefit-cost summary associated with this program is presented

in Table I.


Table I

INFECTIOUS DISEASES OF THE URINARY TRACT, HYPOTHETICAL PROGRAM
   AT CURRENT HEW EXPENDITURE LEVEL, BASED ON THE CURRENT STATE OF THE ART

                                                                 I                                   1
                                                              Short-Term Benefits       Long-Term Benefits


                                                                     Reduction               Reduction In
                               Expenditures               Per Year In      1 End-Stage Uremia
                                                                           1

                                                Total                                      1

           Program       (sI:FL)   ($1,000)  Mortality Prevalence Morbid Days 1 Per Year Cumulative
                                                                           1                    3
I.A. Screening, diagnosis and treatment of
   individuals in short and long-term
   hospitals and nursing homes as well
   as non-hospitalized pregnant females
   and diabetics.

   1. Screening                    1,803     9,017

   2. Confirming  test                      84,457

    3. Treatment                           54,931


                  Sub-Total           1,803   148,405

B. Supportive education and administra-
    tion                         2,000     2,670


                  Sub-Total          3,803    151,075                I


II.   Research                      4,000                     i
                                      5,330

III; Training                             400       530

IV.   Facilities                                           ,i
                                1,000     1,330


                     TOTAL           9,203   158,265        70   3,231,260  15,962,420   1,750   25,850


106

C.  Infectious Diseases of the Urinary Tract, Hypothetical Program
  at Intermediate HEW Expenditure Level, Based on Current State
   of the Art

1.   Introduction

  This program has four components:

1) Screening, diagnosis, treatment, and supportive education and

  administration;

2) Research;

3) Training; and

4) Facilities.

  As illustrated in Figure 2, the total cost for this program is

estimated to be $174,252,000, of which HEW funds would account for

$20,179,000.  A discussion of the various program components follows.

2.  Screening, Diagnosis, Treatment, and Supportive Education and
  Administration

This program is concerned with the screening, diagnosis and treat-

ment of infections of the urinary tract similar to those described in

Section B.2. above.  It has, however, been expanded to include all

females 6 to 9 years of age who can realistically be reached in a

screening program.  It is felt that this group can best be reached

through screening tests applied in elementary schools.

a.  Relevant Population and Program Component Costs

  Because of the difficulties anticipated in attempting to reach

the entire female population 6 to 9 years of age, it is assumed

that a successful program covering a two-year span will be able

                           261          271
to reach about 62% of these individuals.-  Of 8,134,000- females

in this age group, 5,040,OOO will be reached every two years, and

50% (2,520,OOO) of these individuals will be screened each year.


costs ($1,000,000>
174.3








150

100









50









20.2

lm~Training (. 75)

1 Facilities(8.0)1

Diagnosis and
Treatment

(155.3)

Research (7.3)

Facilities (10.

`HEW

TOTAL

-Training (1.0)

Fig. 2.  Infectious Diseases of the Urinary Tract, Hypothetical Program
    Costs at Intermediate HEW Expenditure Level,-Based on the
    Current State of the Art.

106a


  Cost of screening per individual in this additional population

is estimated at $0.25 (as part of a general screening program).

If 2,520,OOO are screened annually, the total cost will be

$630,000 ($126,000 from HEW) yearly.

   Total cost for screening all the population-at-risk, reached

by a general screening program, will be $9,647,000 ($1,929,000

from HEW).

It is believed that 1% of these young females (25,200) will
               291

have significant bacteriuria.-  It is still assumed that only 85%

(21,420) of these individuals can be screened, and that the test
                                                         \-

has associated with it a 5% false positive value so that 22,491

will have positive results.  Confirmatory tests will be necessary

both before and after therapy; therefore, at $7.50 per test, the

total cost for confirmatory tests will be $330,000. For the

entire surveyed population, the cost for these confirmatory tests

will amount to $84,787,000, none of which will come from HEW.

The treatment costs for each of the females 6 to 9 years of age

is estimated at $10.00 for drugs and $15,00 for physicians'

services, or a total cost for all of these individuals of $557,000.

Total treatment costs for all groups surveyed having renal infections

are $55,488,000.

The costs outlined above are minimal and are based on conserva-

tive estimates.  They do not include, for example., intravenous pyelo-

grams and other diagnostic studies necessary for complete diagnosis.
Also note that the overlap in the female population 6 to'9

years of age and the other high-risk groups (that is, the individuals

in short and long-term hospitals, nursing homes and the non-


hospitalized pregnant females and diabetics) has not been taken

into account and some double-counting may be present.

The supportive education and administration portions of this

program component are estimated at a level of $4,000,000 from
                        30/

HEW and $1,330,000 from other sources.- The educational program

involves the extensive education of medical personnel throughout

the country in the proper uses of catheters and antibiotics, the

importance of follow-up studies on individuals with urinary tract

infections, the natural history of pyelonephritis, the proper use

of diagnostic techniques, etc.  The focal centers of the educational

program will be community hospitals from which information will be

disseminated among appropriate personnel.

Total costs for this program component are estimated at

$155,252,000 ($5,929,000 from HEW).

b.  Short-Term Benefits

   In addition to the short-term benefits described in Section B.2.

above, the following benefits are expected to result from the screen-

ing of these young females:

1) Due to the current low mortality rate from urinary infec-

tions in females 6 to 9 years of age, no estimate on the

reduction of immediate mortality is made;

2) A 50% reduction in the prevalence rate from a base of 25,200
to 12,600;z'and

3) A 65% reduction of 311,220 in morbid days from a base of

     32/
478,000.-

Total short-term benefits for all groups surveyed are 70

prevented deaths, a reduction in prevalence by 3,243,860, and a


reduction in morbid days by 16,273,640.

C.  Long-Term Benefits
    -

  (1) Annual Long-Term Benefits

Early diagnosis and treatment of urinary tract infections

in this group of females 6 to 9 years of age will decrease the

number of cases of renal failure by 20 per year.  (A 33%

reduction from a base line of 60 which would eventually have
                                 33/

acquired end-stage uremia without this program).-

   There will be a reduction by 1,770 cases of end-stage
uremia in all relevant groups from a base line of 8,560.%'

(2) Cumulative Long-Term Benefits

351

Approximately 5% (2,520) of the 50,400- females with

bacteriuria could eventually develop significant urinary tract
                         361
infections.  Approximately 40% (l,OlO)- of these individuals

would have developed end-stage uremia.   Since the females in

this age group can be reached at a very early stage of the
                                   371
disease, a reduction in end-stage uremia by 33% (340)- is

anticipated.

About 26,190 cases of eventual renal failure in all

groups surveyed will be avoided.

3.   Research

  Again, clinical and laboratory research are the two major areas

of effort.  Given increased resources, it is realistic to project that

two additional clinical research programs at $500,000 each could be

added to the four existing ones at a total cost of $3,000,000.

Laboratory research project expenditures could feasibly be increased


to $2,000,000 (i.e., an increase of $500,000). Again, a $500,000

project designed to study susceptible sub-groups of patients is

also anticipated.  The total HEW support for research is $5,500,000,

and it is anticipated that about $1,830,000 will be-generated from other

sources.

4.  Training
Training expenditures are estimated to be $750,000 from HEW with

an additional $250,000 from other sources.


5.  Facilities

  In the intermediate health program, it is estimated that HEW will
provide $8,000,000 in addition to an expected $2,670,000 from other

sources.

A benefit-cost summary associated with this program is presented in

Table II.


Table II

INFECTIOUS DISEASES OF THE URINARY TRACT, HYPOTHETICAL PROGRAM
AT INTERMEDIATE HEW EXPENDITURE LEVEL, BASED ON THE CURRENT STATE OF THE ART

                                    7        Short-Term Benefits      Long-Term Benefits
                                                                   -

                                                                   Reduction              Reduction In
                               Expenditures               Per Year In         End-Stage Uremia

                                                                           ?
                                          HEW      Total
           Program              ($1,000)   ($1,000)   Mortality Prevalence Morbid Days  Per Year Cumulative

I.A. Screening, diagnosis and treatment of
   individuals in short and long-term
  hospitals and nursing homes as well
  as non-hospitalized pregnant females,
   diabetics and females 6 to 9 years of
    age.

    1.  Screening

   2.  Confirming

    3.   Treatment


                  Sub-Total

B. Supportive education and administra-
  tion

Sub-Total

II.   Research

III. Training

IV.  Facilities


D.  Infectious Diseases of the Urinary Tract, Hypothetical Program
  at Accelerated HEW Expenditure Level, Based on Current State of
   the Art

1.   Introduction

This program has four components:

1) Screening, diagnosis, treatment, and supportive education and

  administration;

2) Research;

3) Training; and

  4) Facilities.

  As illustrated in Figure 3, the total cost for this program is

estimated at $189,013,000, of which HEW will contribute $27,394,000.

A detailed discussion of the various program components follows.

2.  Screening, Diagnosis, Treatment, and Supportive Education ,and
   Administration

  In addition to the high risk groups surveyed in Section B..2., this

program component has been expanded to include all females 21 years of

age and under.  It is again postulated that the expected rewards from

controlling infectious diseases of the urinary tract in these ,Eemales

would be sizeable enough to merit its consideration.  It is desirable to

reach the majority of females in this age group through schools, colleges,

and various youth programs such as Operation Headstart.


    a.  Relevant Population and Program Component Costs

    A successful program will probably reach approximately 60% of

the relevant female population.  This program will again cover a

two-year span so that one-half of this population will be screened


every year.  Therefore, of the 41,065,OOO females 21 years of age
               381
and under in the U. S.,-  12,319,500 will be screened each year

[i.e., 24,639,OOO (approximately 60%) of the total will be reached in


costs ($1,000,000)

189    -

150

-

50

2

7.4 1

Diagnosis and
Treatment
(165.7)

-

Diagnosis and
Treatment (9.9)

Research (6.5)  :CTraining (.98)
Facilities (10)

HEW

           -


PROGRAM

Research (8. `>

& Training (1.

Facilities
(13.3)

TOTAL

Fig. 3.  Infectious Diseases of the Urinary Tract, Hypothetical Program
     Costs at Accelerated HEW Expenditure Level, Based on the
      Current State of the Art.

llla


two years, and 50% of these, or 12,319,500, will be reached every

year].  It is estimated that about 1% of the females 21 years of age

and under, 246,390, will have significant bacteriuria; therefore,

123,195 will be detected each year.  It is to be emphasized that

this figure is quite conservative since it is known that females

391

12 to 16 years of age have a high incidence of bacteriuria,- and

while no information was available regarding the incidence of

bacteriuria in college-age females, it may be even higher than that

of other school-age females.

   Screening costs in this female population are estimated at $0.25

per person (as part of a general screening program).  If 12,319,500

are screened annually, the total cost will be $3,080,000 ($616,000

from HEW).

   Total screening costs for all the surveyed populations (includ-

ing those described in Section B.2.) will be $12,097,000 ($2,419,000

from HEW.

The number of confirmatory tests required for females 21 years

of age and under will be 109,952 pre-therapy and 104,716 post-therapy
   401
tests,   and the cost for these tests will be $1,610,000 assuming a

rate of $7.50 per test.

   For all the surveyed populations (including those described in

Section B.2.) the total cost for confirmatory tests will be

$86,067,000, none of which is assumed to come from HEW.

   The treatment costs for each female 21 years of age and under

with a confirmed diagnosis of renal infection is estimated at $10.00

for drugs and $15.00 for physicians' services.   This means that the


513

total cost for these affected females is $2,618,000, all of which


comes from sources other than HEW.

  Total treatment costs for all population groups surveyed

having renal infections are $57,549,000.

   The costs outlined are minimal and do not include such items

as intravenous pyelograms and other diagnostic studies which are

necessary for a complete diagnosis.

   Again, the overlap of the female population, 21 years of age

and under, and the other high-risk groups has not been taken into

account and some repetitious counting may be present.

   The supportive education and administrative portion of this

program component is estimated to be $7,500,000 from HEW and

$2,500,000 from other sources.  It is anticipated that the educa-

tional program will be intensified and similar to the one described


in Section C.2.a.

The total cost for this program component is estimated at

$165,713,000 ($9,919,000 from HEW).

b.   Short-Term Benefits

   In addition to the short-term benefits described in Section

B.2.b. above, the following results can be anticipated from a

screening program in females 21 years of age and under:

  1) No estimates were made on the reduction of immediate

  mortality due to the very low mortality rates from urinary

  tract infection in this population;

2) A 50% reduction (61,600) in prevalence rate from a base of

     411
123,195;- and

3) A 65% reduction of 1,521,460 in morbid days from a base


        42/
of 2,340,710.-

Total short-term benefits in all groups surveyed with renal

infections are 70 prevented deaths, a reduction in prevalance of

cases by 3,292,860, and a reduction in the number of morbid days

by 17,483,880.



C.  Long-Term Benefits

  (1) Annual Long-Term Benefits

     As a result of the early diagnosis and administration of

treatment of urinary tract infections, a 33% reduction in the

number of annual cases of renal failure is anticipated.   This

would amount to a decrease of 120 cases from a base line of

360 cases per year.

There will be a reduction by 1,870 cases of renal failure

in all relevant groups from a base line value of 8,860 cases
                               431

which would have occurred without this program.-

(2) Cumulative Long-Term Benefits

Of the 246,390 females with significant bacteriuria who

can be reached by this program, approximately 5% (12,320) would
                                    441

eventually develop significant urinary tract infection.-   Of

this group approximately 40%, 4,930, would eventually die in
         45/
              -
renal failure.   Implementation of the above program would be
                                    461

expected to reduce this mortality figure by 33X, or 1,630.-

A total of 27,480 cases of renal failure in all groups

surveyed would be avoided.

3.  Research

  Given the increased resources of this accelerated program, the number

of clinical research projects could be doubled from the current level of 4


to 8 projects at $500,000 each for a total of $4,000,000.

  Laboratory research expenditures could feasibly be set at $2,000,000,

with an additional $500,000 available for projects designed to study

susceptible sub-groups of patients.

  Thus, the total HEW support for research would be $6,500,000. It

is anticipated that an additional $2,170,000 would be contributed by

other sources.

4.   Training

  Training costs are estimated to be 15% of the research expenditures

i.e., $1,300,500, of which $975,000 comes from HEW, and an additional

$325,500 from other sources.

5.   Facilities

  With an accelerated health program, it is estimated that HEW will

expend about $10,000,000 for facilities in addition to $3,330,000 contributed

by other sources.

A benefit-cost summary associated with this program is presented in Table III.


Table III

INFECTIOUS DISEASES OF THE URINARY TRACT, HYPOTHETICAL PROGRAM
  AT ACCELERATED HEW EXPENDITURE LEVEL, BASED ON THE CURRENT STATE OF THE ART

                                                             Short-Term Benefits       Long-Term Benefits


                                                                   Reduction              Reduction In
                                Expenditures               Per Year In          End-Stage Uremia
                                                                           1
                                         HEW       Total
            Program              ($1,000)   ($1,000)   Mortality Prevalence Morbid Days  Per Year Cumulative

I.A. Screening, diagnosis and treatment of
   individuals in short and long-term
   hospitals and nursing homes as well
   as non-hospitalized pregnant females,
   diabetics, and females 21 years of age
    and under.

   1. Screening                    2,419    12,097

   2. Confirming                           86,067

    3. Treatment                            57,549


                    Sub-Total          2,419   155,713

B. Supportive education and administra-
    tion                           7,500    10,000


                   Sub-Total           9,919    165,713


I.  Research                        6,500     8,670

III. Training                               975     1,300

IV.   Facilities                      10,000    13,330


                      TOTAL          27,394   189,013        70   3,292,860  17,483,880   l.,870    27,480


E.  Infectious Diseases of the Urinary Tract, Hypothetical Program for
Fiscal Year 1975, at Accelerated HEW Expenditure Level, Based on
  Expected State of the Art in 1975

1.  Introduction

  This program has four components:

  1) Screening, diagnosis, treatment, and supportive education and

administration;

2) Research;

3) Training; and

4) Facilities.

The total estimated cost for this program is $215,471,000 of which

HEW will contribute $31,228,000 (see Figure 4).  Under an advanced

state of the art it is assumed that the research efforts undertaken

have made possible 1) more effective antimicrobial therapy, and 2)

a better understanding of the pathophysiology of urinary tract

infection, with new treatment methods for predisposing factors which

sometimes lead to bacteriuria.  A detailed discussion of the various

program components follows.

2.

but

Screening, Diagnosis, Treatment and Supportive Education and
Administration

In 1975 the total U. S. population will have increased by 14$'

there are no anticipated changes in the nature of the relevant

population.

a.  Relevant Populations and Program Component Costs

It is estimated that of a projected 33,227,580 hospitalized

and nursing home residents, 6,645,520 will have significant bacter-
                    481
iuria (a 20% prevalence rate).-  The non-hospitalized pregnant
female population is estimated to be 5,126,580;*' assuming a


215.5

50

31.2

t  Diagnosis &
  Treatment
   (11.3)
  Research
    (7.4)    *-Training
                (1.1)
  Facilities
   (11.4)

HEW

Diagnosis &
Treatment
(188.9)

Research
  (9.9)

Facilities
  (15.2)

TOTAL

/Training
   (1.5)

Fig. 4.  Infectious Diseases of the Urinary Tract, Hypothetical Program
     Costs for Fiscal Year 1975, at Accelerated HEW Expenditure Level,
     Based on Expected Advanced State of the Art in 1975.

llha


prevalence rate of 6% for bacteriuria, 307,590 persons will have

positive screening tests.  The non-hospitalized diabetic population
           501

will be 2,761,080-  and approximately 414,160 will have

bacteriuria (assuming a 15% prevalence rate in the diabetic

population).  While it is possible that significant improvements

in the treatment and diagnosis of diabetic.s will have occurred,

this assumption was not made.  It is anticipated that 14,044,230

females under 21 years of age will be scresened yearly; 140,440

of these women will have significant bacte,riuria, assuming a 1%
          511
prevalence rate.-  (Note it is still assumed that only 60% of

the females 21 years of age and under can 'be reached, and that the

screening program will cover a two-year sp,an.)

  Cost of screening will be $13,790,000 ($2,758,000 to be borne

by HEW).  It is still assumed that the cost per test under a general

screening program will be $0.25, and this (cost is applied to the
       521
55,159,440-  individuals to be screened each year.

  The cost of confirmatory tests remains at $7.50 per person.

Total cost is approximately $98,150,000, excluding a second repeat

test for false-positive patients.

  Treatment costs also remain the same, i.e., $10.00 for drugs

for those individuals who are already under a physician's care. It

is estimated that there are.6,262,180 of these individuals yielding

a cost of $62,622,000.  For those individuals who would not have

been under a physician's care (the female population 21 years of age

and under), $15.00 per individual for physicians' services is added.

The cost of treatment for this group is $2,984,000 (119,374 x $25). 531


- Total cost of treatment is thus estimated to be $65,606,000.

HEW is not responsible for the cost of confirmatory tests or

treatment.

Total cost for this initial portion of the program component

is $177,511,000, of which $2,758,000 is to be borne by HEW.

Support for education and administration is estimated to cost

$8,550,000 for HEW, to include a more extensive educational program

to reach the increased population.  An additional $2,850,000 will

come from outside sources.

   Therefore, the total cost for this program component is

$188,911,000, of which $11,308,000 comes from HEW.

b.   Short-Term Benefits


   The estimated short-term benefits are as follows:

  1) From a base line of 7,750 deaths in the group surveyed

which would have occurred in the absence of any program,
                         541

  a reduction of 80 deaths is estimated;-

2) It is estimated that there will be an 85% reduction

  (5,630,780) in prevalence from 7,507,710 cases [35 of the 85%

  (1,876,930) can be attributed to advances in the state of
        551
  the art];-  and

3) It is estimated that the number of morbid days will be

reduced by 85% (26,064,430) from a base line figure of

30,664,040 (20 of the 85% reduction, i.e., 6,132,810 is
                                561

attributed to advances in the state of the art).-

C.  Lens-Term Benefits

  (1) Annual Long-Term Benefits

     It is estimated that approximately 7,500 of the group


surveyed per year will have developed end-stage renal failure

without the program.  Ideally this program would reduce this

number by 55%, or 4,125 per year [of which 2,250 (approximately

30 of the 55% reduction) are due to advances in the state of
      571
the art].-

(2) Cumulative Long-Term Benefits

   About 5% of the individuals with bacteriuria would have

developed significant urinary tract infections in the absence

of any program.  Approximately 40% of these persons would

eventually die from uremia.  Within the relevant population,
                                   581
there would be 7,658,160 individuals having bacteriuria.-

It can then be said that some 382,400 will probably develop

significant urinary tract infections and 40%, or 153,000, of

these would eventually die from uremia.  It is estimated that

the number of deaths resulting from end-stage kidney failure

can be reduced by 55% or 84,150 (approximately 30 of the 55%,

or 45,900, of the reduced number of deaths is due to advances
                591

     in the state of the art).-

3.   Research

  Research expenditures will be increased in amount to $7,410,000

which will come from HEW, and an additional $2,470,000 to come from

other sources.  It is anticipated that a cure :Eor urinary tract

infections may be found through the development of new antibiotics and

new treatment methods for predisposing factors which sometimes lead TO

bacteriuria.

4.  Training

  Money expended for training purposes will total $1,480,000, about


15% of that spent for research.  Of this amount, $l,llO,OOO will come

from HEW and an additional $370,000 from other sources.

5.  Facilities

  In an accelerated Health Program it is estimated that HEW will con-

tribute $11,400,000 for facilities,  Additional sources wilt1 contribute

$3,800,000.

A benefit-cost summary associated with this program is presented in

Table IV.                         gJ
F.   Benefits Denendent on New Research Developments
An annual reduction by 1,876,930 in the prevalence rate of renal infection

and by 6,132,810 in the number of morbid days will be the short-term effects of

new research developments.  These statistics take into account a postulated

14% increase in the population of the U. S. from 1966 to 1975.  Benefits based

on 1966 population figures reveal a reduction in prevalence by 1,646,430 and
in the number of morbid days by 5,379,660.

  In assessing the annual long-term benefits dependent on new developments,

it is estimated that there will be a reduction of 2,250 cases of end-stage

kidney disease per year, (1,970 cases based on 1966 U. S. population).

Cumulative long-term benefits reveal that 50,650 (44,430 based on 1966 U. S.

population) cases of renal failure will be avoided with the advent of new

developments and techniques concerned with chronic kidney infections.


Table IV

  INFECTIOUS DISEASES OF THE URINARY TRACT, HYPOTHETICAL PROGRAM FOR FISCAL YEAR 1975
AT ACCELERATED HEW EXPENDITURE LEVEL, BASED ON EXPECTED ADVANCED STATE OF THE ART IN 1975

1                      .
                          Short-Term Beneifts       Long-Term Benefits


                              Reduction               Reduction In
   Expenditures               Per Year In          End-Stage Uremia

           Program              ($1,000)   ($1,000)   Mortality Prevalence Morbid Days  Per Year Cumulative

I.A. Screening, diagnosis and treatment of
   individuals in short and long-term
   hospitals and nursing homes as well
   as non-hospitalized pregnant females,
   diabetics, and females 21 years of
   age and under.

   1. Screening                    2,758    13,790
   2. Confirming                          98,115

    3. Treatment                             65,606


                   Sub-Total          2,758    177,511

B. Supportive education and administra-
    tion                           8,550    11,400


                   Sub-Total          11,308   188,911


II.   Research                         7,410     9,880

III. Training                        1,110     1,480

IV.   Facilities                      11,400    15,200


                      TOTAL          31,228   215,471        80   5,630,780   26,064,430   4,125   84,150


III.  HYPERSENSITIVITY DISEASES'OF THl3 KIDNEX

x, Introduction

This section describes program efforts projected to control renal disease

resulting from hypersensitivity phenomena.
               611
In 1966, an estimated U,719-- deaths resulted from kidney disease s,ssoci-

sted with kWpersensitivity reactions; 106,000 individuals are estimated to
have had hypersensitivity diseases of the kidney, requiring 4,074,OOO deys of
restricted activity, 1,834,OOO days of bed disability, as well as 77'7,000
       627
work-lOS8 days.-

Four programs are considered in this analysis and discussed in det&l

below (see Chapter 5, Research Methodology).

B.  Kidney Diseases Related to Hypersensitivity Phenomena, Hypothetical
Program at Current HEW Expenditure Level, Based on the Current State
  of the Art

1.  Introduction

  This program has four components:

1) Education and administration;

2) Research;

3) Training; and

4) Facilities.

The total cost for this program is estimated to be $9,975,000 of

which HEM's share is $7,480,000.  Figure 5 illustrates costs for the

various program components, and they are discussed below.

2.  Education and Administration

In order to bring an effective educational program to physicians,
it is necesssry to supply the approximately 7,000 hospitals in the U. S.
with appropriate materials and other educational support. Elstimating
a cost of $140 per hospital, approximately $l,OOO,OOO will be needed for


costs ($1,000,000)

150

100

50

10.3
7;s

Education and
Administration
  (I,53

Research (5.2)


    HEW

Education and
Administration

Fig. 5. Kidney Diseases Related to Hypersensitivity Phenomena,
    Hypothetical Program Costs at Current HEW Expenditure
    Level, Based on Current State of the Art.

121a


instruction in this area of kidney disease as part of a general educa-

tional progrsm.  In addition, about $500,000 will be required for the

administration and implementation of this program. The total cost for

HEN is then estimated at $1,500,000.  An additional $500,000 is expected

from other sources.

  Under the current state of the art postgraduate physician education

seems to be the most effective approach for achieving immediate benefits.


    a.  Short-Term Benefits

    It is estimated that this educational program would decrease

  the immediate annual mortality due to hypersensitivity diseases by
                          63/
  approximately 5% (610) from a base line of X2,719- deaths per year.

  This figure is based on the assumption that improved understanding

  of diseases such as acute glomerulonephritis, and improved knowledge

  of fluid, electrolyte, and steroid therapy will have some impact on

  the immediate mortality from diseases associated with hypersensitivity

  phenomena.


   b.  Long-Term Benefits

    Under the present state of the art, no long-term benefits are

  anticipated.

3.  Research

  This most important program component is separated into clinical and

laboratory research efforts.

   a. Clinical Research

    Following are some areas of disease which need clarification

  and study to determine their significance in hypersensitive renal'

   disease:


J-23

1) Minimal persistent proteinuria;

2) Orthostatic proteinuria;

3) Childhood nephrotic syndrome;

4) Adult nephrotic syndrome;

5) Acute glomerulonephritis;

6) Systemic lupus erythematosus;

7) Miscellaneous collagen diseases; and

8) Any other related hypersensitivity diseases having renal


   involvement.

  The estimated cost for each study area is $500,000, yielding
a total cost of $4,000,000 ($3,000,000 from HEW).

  Following are some comments on the present status in each of

the above study areas:

1) Several universities have been approached on the possibility

  of conducting cooperative studies on the diseases listed

  above and have expressed interest in them.  No further

  progress has been made due to a shortage of funds.

2) The Air Force is currently studying orthostatic proteinuria

  at Lackland Air Force Base, Texas.

3) There is an international cooperative study being conducted

  on the childhood nephrotic syndrome under the direction of

  Dr. Henry Barnett of the Albert Einstein Medical Center in

  New York City.

4) There is no coordinated activity eon the adult nephrotlc

  syndrome at the present time in the United States. However,

  in Great Britain, there is a stud;y sponsored by the British


    Medical Research Council on the controlled treatment of

     adult nephrotics with steroids.
5) There is a loose cooperative study on acute glomerulone:phritis

    under way in New York City.  There is also a study being

    supported on the island of Trinidad which is designed to

    follow patients with acute glomerulonephritis. The re-

    surgence of the Red Lake epidemic of acute glomerulonephritis
   is also under study by Dr. Wanamaker's group at the University

      of Minnesota.
6) There is a loose cooperative study by several university

    centers emphasizing the pathology in nephritis resulting

    from systemic lupus erythematosus.
7) Other disease processes that might be grouped under the

    heading of hypersensitivity diseases are sub-acute glomerulo-

     nephritis, chronic glomerulonephritis, serum sickness

     nephritis, and nephrotoxic nephritis in animals.

b.  Laboratory Research

  There are at present approximately 30 immunology research units

in existence.  It is estimated that approximately 15 of these units
are currently engaged in work which is applicable to hypersensitivity

diseases of the kidney.  The total contribution of funds for re:Levant
studies to these laboratories would be approximately $1,500,000
($lCO,OOO each) per year, of which HEN would contribute $l,l25,000.
In addition, it is estimated that an additional $1,500,000 ($1,125,0OO
from HEX) should be made available for grant support of individual


125

projects in other laboratories. At an average cost of $25,000

  each this smount would support the work of 60 investigators.
   It is assumed that the total of $7,000,000 as described in the

  above categories will come from both federal and private funds, with

  the majority coming from HEW.

4. Training

  It is anticipated that each of the 15 involved immunology laboratories

would provide training for two research fellows per year.  The cost for

this progrti would be approximately $5O,OOO per laboraWry per year,- 641
or a total of $75O,OOO for the whole program ($560,000 from HEW).

5*  Facilities

  In order to continue expanding research capabilities and updating

the necessary equipment, it is estimated that 15'$ of the yearly cost of

laboratory research operations will be spent. The total cost of equip-

ment updating for 15 laboratories amounts to $225,000 per year (15$ of
which, $170,000, comes from HEW).

6.  Summary

  The preceding discussion and estimates presume activity on a level

considerably above the current status.  There -Its a substantial initial

cost in achieving the new elevated level of activity.  Principal among

these costs is the expense of constructing and providing adequate facilities.

This amount should not be confused with the facilities estimate discussed

above which is for the improvement of equipment intended to keep research

workers supplied with the best equipment for their varied programs.

A benefit-cost summary associated with this program is found in

Table V.


Table V

KIDNEY DISEASES RFZATEDTO HYPERSENSITIVITY PHENOMENA, HYPO'IW3TICALPROGW AT CURRENTHEW
           MPEN-DITURELEVEL,EUSEDONTHE CURRENT STKI'% OF THE ART

Program

I.   Education and administration


II.  Research

III. Training


IV.  Facilities


                       TOTAL

Expenditures

1,500     2,000

5,250     7,000


560        750


170       225

7,480

Total
($1,000)

i

Short-Term Benefits

Reduction
Per Year In

Mortality Prevalence  1 Morbid Days   Per Year

=I
Cumulative

+

9,975       610 - - - -



c.  Kidney Diseases Related to Hypersensitivity Phenomena, Hypothetical
  Frogrem at Intermediate REW Expenditure Level, Based on the Current
State of the Art

1.  Introduction

  This program has four components:

1) Education and administration;

2) Research;

3) Training; snd

4) Facilities.

The estimated total cost for this program is $26,670,000. HEW'S

share is estimated at $20,000,000. Figure 6 graphically iresents the

costs for this portion.  A discussion of the various program components

follows.


2.  Education and Administration

Under an intermediate, postgraduate physician

HEW will contribute $2,5oO,ooO, and an additional

support.  An additional $l,OOO,OOO will be needed

education program,
$500,000 for administrative

from other sources*

There are no immediate benefits expected from this new educational effort,

although long-term benefits will be significant; therefore, the smue
mortality reduction figure of 610 (see Section B.2.) is used.

3. Research

  With an intermediate level of financial support, clinical research
funds can be increased to $~,OOO,OOO ($4,500,000 from HEW). This
represents twelve large scale studies at $500,000 each, rather than

eight as described abave in Section B.3.

  To provide more rapid developments, an increase from fifteen to

twenty laboratory research centers in conjunction with an increase in

the amount of financial support for each of the twenty centers, will be


costs ($1,000,000)

150

100

Education and

PROGRAM

Education and
Administration
  (4.0)     I

*I Training
(1.0)
     TOTAL

Fig. 6.  Kidney Diseases Related to Hypersensitivity Phenomena
    Hypothetical Program Costs at Intermediate HEW Expenditure
    Level, Based on the Current State of the Art.

126a


supported by an intermediate health progrsm.  Total cost would then be.

$3,OOO,OOO of which HEW would contribute $2,25O,oOo.
Individual research grant funds would be increased from $1,5OO,OOO

to $2,000,000 per year, representing an increase in number from 60 to

70 per year at an average smount of $28,500 each. HEWS contribution

would be $1,5OO,OOO.

  All research efforts would total $ll,OOO,OOO with $8,25O,ooO coming

from HEW; the remainder coming from other sources.

4.  Training

  Training for research would be extended to include 20 immunology

research laboratory centers, which will provide for the training of two

fellows per center at a cost of $50,000 per center. Total expenditures
are estimated to be $l,OOO,OOO per year ($75O,OOO from HEW).

5. Facilities

It is estimated'that the yearly cost of expansion for the research

program and the updating of equipment will require approximately
$10,670,000 ($~,OOO,OOO from HEW).

A benefit-cost summary associated with this progrsm is found in

Table VI.


Table VI

KIDNEY DISEASES RFUQEDTO HYFEZSEXKWPIVI~ PHENOMENA, HYPOTHETICAL PROGFlAM AT INTERMEDIATE
         HEWMF'ENDITUlW LEVEL, BASED ONTHEiUJRRENT STATE OFTHEART

.                       I                                   ,

                      ,        Short-Term Benefits       Long-Term Benefits
                      I,
                            Reduction             Reduction In
   Expenditures               Per Year In          End-Stage Uremia

Program

I.   Education and administration


II.  Research

III. Training


IV.  Facilities


                      TOTAL

(Sl:ZO)

3,000

8,250

750

8,000

Total
($1,000)

4,000

11,000

1,000

10,670

26,670

Mortality

610

Prevalence Morbid Days  Per Year Cumulative


D.  Kidney Diseases Related to Hypersensitivity Phenomena, Hypothetical
  Progrsm at Accelerated REW Expenditure Level, Based on the Current
   State of the Art

1.  Introduction

This program has four components:

1) Education and administration;

2) Research;

3) Training; and

4) Facilities.

The estimated total cost for this progrsm is $31,830,000. HEW's

share is estimated to be $23,875,000. Figure 7 shows the costs for this

program and below follows a discussion of the various program components.

2.  Education and Administration

No changes in the educational and sdministrative efforts sre sntici-

pated under this accelerated program.  m3w tin provide $2,5oo,oqo for

educational support and an additional $500,000 for administrative support.

Approximately $1,OOO,OOCl will be assessed to institutions other than HEW.

No immediate benefits ere expected, and the mortality reduction figure of

610 (see Section B.2.) is used sgain.

3. Research

  With ample support, clinical research funds could be increased to
$8,ooo,ooo ($6,ooo,ooo from m).  This would represent 16 large scale

studies rather than eight as envisioned under the current HEW budget

level.

Daboratory research would remain at the level anticipated for an

intermediate program at a total cost of $3,000,000 ($2,25O,OOO from


zests ($1,000,000)

150

100

                         Education and
                           Administration

Education and              (410)
Administration                         V
(3;O)                        Research
     V                      (13.5)
  Research
  (10.1)                       A-Training (1.0)
       +-Training (.8)
Facilities                     Facilities

  (10.0)                    (13.3)

HEW

PROCRAM

TOTAL

Fig. 7.  Kidney Diseases Related to Hypersensitivity Phenomena,
    Hypothetical Program Costs at Accelerated HEW Expenditure
     Level, Based on the Current State of the Art.

128a


The number of individual research grants would be increased from

60 to 80 at an average cost of about $31,000 each and a total cost of

approximately $2,5OO,OOO per year ($1,870,000 would be HEW's responsi-

bility).

Total efforts aimed at research would smount t0 $13,500,000

($10,125,000 to come from HEW).

4. Trainina;

Expenditures on research training will remain at $l,OOO,OOO ($750,000
from HEW), the same level as anticipated for the intermediate program,

5. Facilities

With ample support fm HEW, it is expected that $13,330,@00 will

be expended on facilities with $10,000,000 expected to come frm HEW

and $3,330,000 from other sourcesm

A benefit-cost sumnary associated with this program Is found in

Table VII.


Table VII

KIDNEY DISEASES RELATED TO HYPERSENSITIVITY PHENOMENA, HYPOTHETICAL PROGRAM
      AT ACCELERATED HEW EXPENDITURE LEVEL, BASED ON THE CURRENT STATE OF THE ART

           Program



I.   Education and administration


II.  Research

III. Training


IV.   Research


                      TOTAL

                      Short-Term Benefits      Long-Term Benefits


                           Reduction              Reduction In
  Expenditures               Per Year In          End-Stage Uremia
(SlyEJ)     Total
      ($1,000)  Mortality Prevalence Morbid Days Per Year Cumulative


3,000     4,000

10,125    13,500


   750     1,000

10,000    13,330

23,875    31,830      610 - - e m


E.  Kidney Diseases Related to Hypersensitivity Phenomena, Hypothetical
Program for Fiscal Year 1975, at Accelerated HEW Expenditure bevel,
  Based on Expected Advanced State of the Art in 1975

1.  Introduction

  This program has five components:

  1) Prevention of acute glomerulonephritis;
2) Early detection of disease (manifested by proteinuria), treatment

    of diseases associated with hypersensitivity phenomena, and

    supportive education and administration;

3) Research;

4) Training; and

5) Facilities.

The estimated total cost for this program is $334,420,000 of which

HEW will expend $~,320,000.  Figure 8 illustrates costs associated

with the various program components.

  Advances in the state of the art which are anticipated by 1975,

have been broken down into three separate categories. They are:

1) Acute glomerulonephritis-- in T,<hich primary preventive measures

will be available (e.g., a vaccine and/or effective treatment

of streptococcal infections).

2) Chronic glomexxlonephritis-- which is heralded by patients with

  proteinuria and in which secondary preventive measures may be

  available; and

3) Other diseases --such as chronic sclerosing nephritis, the
collagen diseases (e.g., lupus erythematosus, scleroderma, etc.)
in which secondary preventive measures may be available, and's
miscellaneous group of renal diseases (e.g., smyloidosis).


costs ($1,000,000)

334.4

      ,


1 50









1 00









77.3









50

I
   Vaccine
  (40.0)

Diagnosis and
Treatment
(13.0)

Research

HEW

PROCRAM

Diagnosis and

Treatment

Research
(16.6)

4 I rainitig (2.5)

Facilities
(13.3)

TOTAL

Fig. 8.  Kidney Diseases Related to Hypersensitivity Phenomena,
    Hypothetical Program Costs for Fiscal Year 1975, at
    Accelerated HEW Expenditure Level, Based on Expected
      Advanced State of the `jrt in 1975.

130a


  No detailed analysis for the class of Other Diseases, namely
collagen disorders and the miscellaneous group of renal diseases, has

been undertaken.

2.  Prevention of Acute Glomerulonephritis

  Two possible advances in the next 10 years sre analyzed in this

report.  These are:
1) The development of a vaccine to prevent Group A beta-hemolytic
   streptococcal infections (especially Type 12); and/or
2) The development of an efficient means for the early detection

  of beta-hemolytic streptococcal infections and the prevention

  of subsequent glcxuerulonephritis through effective therapy.

a. Develolplent of a Vaccine to Prevent Streptococcal Infection
(1) Relevant Population and Program Component Costs
                       65/
    The assumption is made that 200,000,000- persons would

be vaccinated in 1975 at a cost of $1.00 per individual. Total
cost for this vaccination program is estimated at $200,000,000
($40,000,000 to come from HEW).

  (2) Short-Term Benefits

Short-term benefits are estimated as the following:

1) From an estimated base of 650- deaths resulting from
                 w

  acute glomerulonephritis which would have occurred

  without a vaccination program, a 959 reduction in

  mortatity, i.e., 620 avoided deaths, is anticipated.
2) There will be a 95$ reduction in the number of cases
of acute glomerulonephritis (i.e., 52,250) from an

  estimated base line of 55,000 cases.


             67/
3) Assuming &I morbid days- per case of acute glomerulo-

nephritis, a base line of 2,200,OOC morbid days is

calculated using 55,000 cases as a reference.  Morbid

days will be reduced by 95$, or 2,09o,OCO, with this

program.

(3) Long-Term Benefits

  (a) Annual Long-Term Benefits
    It is estimated that without a vaccine 5s (2,750) of

the 55,000 individuals with acute glomerulonephritis

eventually would have developed end-stage uremia.  Assuming

that each new patient with acute glomerulonephritis which

progresses to the chronic stsge will have a normal age-

life span, then the yesrly death rate from hypersensitivity
diseases will be reduced by 2,610. The vaccine will

reduce the number of cases of acute glomerulonephritis by

95% be., 2,610 of 2,750).

(b) Cumulative Long-Term Benefits

  Assuming that without a vaccine approximately
   681
100,~ of the population eventually would have developed

end-stage uremia due to acute glomerulonephritis, approx-
imately 95,000 (95s of 100,000) persons will have avoided

death resulting from end-stsge uremia.

b.  Alternate Detection and Treatment Program

  An alternative possibility is the development of an effective

means to detect and to provide adequate treatment for immunologic


133 '

reactions in the kidney resulting from streptococcal infections.

Two possibilities are presented below:

  1) Early detection of streptococcal infection and immediate

    therapy with penicillin may prevent the serious sequelae

     resulting frcxn acute glomerulonephritis; or it may succeed

    in interrupting an epidemic of acute streptococcal infections,

    thereby reducing the possible incidence of glcxnerulonephritis;

      and

2) Advances in imrmnosuppresslve therapy could prevent cases

  of acute glanerulonephritis which arise from nephritogenic

  strains of streptococci.

  This progrsm would be directed toward a population in which en

epidemic of nephritogenic beta-hemolytic streptococcal infection is

in progress.  Therefore, a program of close epidemiologic&l. surveil-

lance of the population susceptible to streptococcal infections, and

the rapid institution of immediate treatment procedures would be

undertaken.

  A 2C$ reduction in mortality would be expected lowering the

number of mortalities due to the acute disease process by 130 per
ye&/ A reduction in prevalence rates by 30$ would decrease the

number of cases by 16,500 per year from a base line of 55,000; the

number of morbid days would be decreased by 30$, or 660,000 days

per year, from a base line of 2,200, cxloP/  The total effect on the

2,750 individuals who would have developed end-stage uremia each

would be a reduction by 36, i.e., 830 cases, with this progr SIG'

Cumulative long-term benefits would be 30,000 avoided cases of


134

  end-stage uremia (30$ of the estimated 100,000 who would have
developed kidney failure eventually)@  These alternative benefits

  have not been included in the summation of the program analysis.

3.  Proteinuria

  A second approach in preventing renal hypersensitivity disease would
be an attempt at the early detection of persistent proteinuria. It is
assumed that this phenomenon represents an early stage of renal disease
in which the filtering apparatus of the nephron is malfunctioning, giving

some indication of impending chronic nephritis.  The major objective of

the program is to develop an effective means for the early detection of
persistent proteinuria, to identify those cases in which proteinuria
signifies renal disease, and to devise adequate therapy which will

interrupt the disease process, thereby preventing progression to a

state of renal failure.  It will be assumed that under this advanced

state of the art, a means of therapy has been developed which is
effective in 5C$ of those cases treated.

  a. Relevant Population and Program Component Cost

   Assuming that 150,000,000 people can be screened each year via

  periodic physical examinations, multiphasic screening programs, etc.,
                                   73/
2$ (3,000,OOO of these) will have a positive test for proteinurisr
   Of 3,000,OOO patients with a positive test, approximately 20$,
600,000, will be expected to have confirmed proteinuria as shown by

  more refined and more expensive tests.  The confirmatory test costs

  $1.00; therefore, the total cost is $3,000,000 since each individual
                               74/

with a positive screening test must have a confirmatory test-r


  Of the 600,000 confirmed positive patients having proteinuria,
it is anticipated that additional studies will establish 20$ (120,000)
as having persistent proteinuri&'  The estimated cost for these
additional studies is $5.00 per test for a total cost of $3,000,000
($5.00 x @Wm.

  For each of these 120,000 individuals a complete diagnostic

work-up including:  urine analysis, amount of total protein excretion,

studies of renal functions such as clearance and concentrating abili-
ties, roentgen studies (to include a flat film of the abdomen,
intravenous pyelogrsms, and possibly retrograde pyelogrsms if
necessary), and in some instances a renal biopsy to be examined

under the electron microscope is necessary to establish a definite

cause of proteinuria.  The estimated cost is $500 per individual
study for a total cost of $60,000,000.
  Total costs for confirming tests amount to $66,000,000, none

of which is expected to cOme from HEW.

  One-third of the 120,000 individuals with confirmed persistent
proteinuria (i.e., 40,000), could potentially develop debilitating
renal diseass' Of this number about 50$ (20,000) are estimated

to have renal disease associated with hypersensitivity phenomena.
It is estimated that a single therapeutic course would cost $100
per patient for a total of $2,000,000.
Total costs for this program component are $98,000,000
($2,000,000 of which is to be borne by HEW).
Support for education and administration is estimated to cost
HEW $3,000,000 with $l,OOO,OOO coming from other sources*


136

4.

b.  Short-Term Benefits

  Short-term benefits for individuals having diagnosed renal

disease with hypersensitive origin followed by some form of

treatment are:

1) A reduction of l$, or approximately 150 deaths, from a
           777
  base line of 14,500-- expected annual deaths in patients

with hypersensitivity diseases of the kidney;

2) A reduction of 56, or 10,000 cases, from a base line of

  20,000 cases diagnosed as hypersensitivity disease of the
kidney;E/ and

3) A reduction of 65$, 520,000 days, from an estimated

800,000 morbid day BTe/

c. Iong-Term Benefits

(1) Annual Long-Term Benefits

       The annual death rate could be reduced by 50$1 based on the

  assumption that new cases are diagnosed each year and that therapy

   is effective in one-half of the individuals.  The therapeutic

  results should improve as cases can be detected earlier; and
                             w
ultimately a decrease of 6,000 from a base line of l2,000-

  cases of fatal end-stage uremia per year could be effected.
(2) Cumulative Long-Term Benefits
                          W
    From an expected base of 450,000 individuals- having

  confirmed persistent proteinuria who would have developed
end-stage uremia eventually, a reduction of 56, or 225,000,

  is anticipated in an accelerated HEW health program.

Total Screening, Diagnosis and Treatment Costs

Total costs for screening, diagnosis, and treatment are estimated

to be $102,000,000 ($13,OOO,OOO from HEW).


337

5. Total Short-Term Benefits

Total short-term benefits resulting from the control of acute

glomerulonephritis using a vaccine and from the detection and control

of proteinuria are as follows:

  1) A reduction in immediate mortality by 'j"j'O per year;

  2) A reduction in the number of cases by 62,250; and

  3) A reduction in the number of morbid days by 2,610,ooo.

6. Total Long-Term Benefits

Total long-term benefits resulting from the control of acute

glomerulonephritis using a vaccine and from the detection and control

of proteinuria are an annual reduction of,8,610 cases of fatal end-stage

uremia and cumulative long-term reduction of 320,OOO.

7.  Research

  Research programs under the advanced state of the art sre anticipated

to increase so that HEW's expected level of effort w-J.11 be $12,450,000;

$4,150,000 will come from other sources.

8. Training

  Funds needed for training will approximate 15s of the amount spent

on research, i.e., $2,493,000, of which $1,870,000 will come from HEW

and $620,000 will come from other sources.

9. Facilities

HEW will expend about $10,000,000 for facilities and an additional

$3,330,000 will come from other sources.

10.  Estimated Benefits Dependent Upon Research

   Benefits dependent on new disease control techniques are;

a) Short-Term Benefits:


338

1) A reduction in immediate mortality by 770 deaths (680
                  82/
based on 1966 U. S. population);-

2) A reduction in the number of cases by 62,250 (54,610

based on 1966 U. S. population); and.

3) A reduction in the number of morbid days by 2,610,OOO

(2,289,470 based on 1966 U. S, population).

b) Long-Term Benefits:

1) An annual reduction of fatal end-stage uremia by 8,610

cases (7,550 based on 1966 U. S. population); and

2) A cumulative reduction of fatal end-stage uremia by

32O,OOO cases (based on 1966 U, S. population).

A benefit-cost summary assokated with this program is found in

Table VIII.


Table VIII

KIDNEY DISEASES RELATED TO HYPERSENSITIVITY PHENOMENA, HYPOTHETICAL PROGRAM FOR FISCAL YEAR 1975
  AT ACCELERATED HEW EXPENDITURE LEVEL, BASED ON EXPECTED ADVANCED STATE OF THE ART IN 1975

Program

I.  Attack on acute glomerulonephritis
  streptococcal vaccine

II.  Proteinuria, screening, diagnosis and
   treatment, and supportive education
   and administration:

    1.  Screening

    2.  Confirming test for persistent
     proteinuria
a
:    3.  Confirming test for renal compli-
       cations

   4.  Treatment for renal complications

                   Sub-Total

5.  Education and administration


               Sub-Total

III. Research

IV.  Training

V.   Facilities

TOTAL

Expenditures

(sl::o)

40,000

10,000

10,000

3,000

13,000

12,450

1,870

10,000

77,320   334,420       770   62,250    2,610,OOO   8,610    320,000

Total
($1,000)

200,000

30,000

6,000

60,000

2,000

98,000

4,000

102,000

16,600
2,490

13,330

Short-Term Benefits       Long-Term Benefits

Reduction              Reduction In
Per Year In          End-Stage Uremia

Mortality  Prevalence  lorbid Days  Per Year  Zumulative


IV.  KIDNEY DISEASES RELATED TO HYPERTENSIVE VASCULAR DISEASES

A.  Introduction

This section pertains to programs needed to control renal diseases

associated with hypertension.  It is assumed throughout the discussion that

the amelioration of hypertension will result in a significant reduction in

             jg/
associated renal disease.

In 1966, 71,347 death+' are estimated to have had hypertensive vascu-

lar disease as the underlying cause of death.  Of this group it is estimated
         85/

that about 3Oc were caused at least partially by serious renal sequelae.

In 1966, some 11,430,OOO individuals are estimated t.o have had hyper-

tensive vascular disease ;.associated with these were 181,280,OOO days of

restricted activity, 68,580,OOO days of bed disability, and 11,330,OOO
               861

work-loss days resulted.-

Three programs are considered in this analysis (see Chapter 5, Research

Methodology) and are described in detail below.

B.  Kidney Diseases Related to Hypertensive Vascular Diseases, Hypothetical
Program at Current HEW Expenditure Level, Based on the Current State of
  the Art

1.  Introduction

This program has four components:

1) Diagnosis, treatment, supportive education and administration;

2) Research;

3) Training; and

4) Facilities.

The total estimated cost for this program is $419,440,000 ($40,272,000

specifically for associated renal problems).  HEW would account for

$9,180,000, all of which would be used to control the renal complications


of hypertension.  Figure 9 illustrates the program expenditures for

associated renal problems.  A discussion of the various program

components follows.

2.  Diagnosis, Treatment and Supportive Education and Administration

  Screening, diagnosis and treatment are aimed at individuals 17 years

of age and over who have potentially curable (non-essential) hypertension

or currently non-curable (essential) hypertension.

a.  Relevant Population and Program Component Costs

  This program component provides for the extension of complete

care to individuals with known hypertension.  HEW would provide

financial support for education and administration of this program.

Various studies have shown that between lo-20% of all hyper-
                                  871

tensive patients have potentially curable hypertension.-  It is

estimated that approximately 15%, 1,450,000, of the known total

hypertensive population (9,330,OOO in 1966) have curable (non-essential)

hypertension.  Of this number, it is estimated that about 450,000

are presently receiving adequate treatment.  With this program, an

additional 450,000 would receive adequate treatment over a five-year

period.  This program would provide treatment for 90,000 of these

patients each year.

  Since this is a population of known hypertensives and no screening

test would be necessary, the cost for definite diagnosis and treatment

of a specific type of hypertensive vascular disease would be $1,000

per patient per year.  The total cost is then $90,000,000 per year,
                    881

and an estimated 10% ($9,000,000>- of this amount is to be used to

treat associated renal hypertensive disease.


100

50


40.3









9.2

Dianxiosis and
Treatment (4.0)

PROGRAM

Diagnosis and
Treatment
(33.4)

Research (5.1)

            ,
TOTAL

Training (.5)
CFacilities (1.3)

Fig. 9.  Kidney Diseases Related to Hypertensive Vascular Diseases,
    Hypothetical Program Costs at Current HEW Expenditure Level,
     Based bn the Current State of the Art.

1

40a


No screening test is required for the currently known non-

curable hypertensives.  The treatment cost for each of these
                         B/

individuals is estimated at $200.00 per year.   In addition, it is

anticipated that this program will provide for an increase of 20%
       go/
(1,586,000)-  in the number of patients being adequately treated.

Therefore, total treatment costs for these individuals would be

$317,200,000.             911
       Approximately 64b of this amount, $19,032,000 would

be used for the treatment of associated renal disease.

  Total cost for the above program is $407,200,000 ($28,032,000

of which is for associated renal problems).  These costs are not to

be borne by HEW.

  The supportive education and administration component involves

the postgraduate education of physicians as well as the community

on kidney malfunction as it is related to hypertensive disease.
Technical support as well as some financial support is also included.

It is estimated that $4,000,000 is the minimum amount needed under

the 1966 HEW funding level to activate this program component.

Approximately $1,330,000 will be generated by institutions and sources

other than HEW.

  Total cost for this program component is $419,440,000

($40,272,000 used for associated renal disease).  Total HEW expendi-

ture for program component 2.a. is $4,000,000, all of which is

employed for treatment of kidney disease.

b.  Short-Term Benefits

  The following are estimated short-term benefits:

  (1) Known Potentially Curable (non-essential) Hypertensive
       Patients:


t42

921

1) Of a total population of 90,000- having non-essential

hypertension, a 60% reduction in the immediate mortality

rate is expected (i.e., 340 of the estimated 570 normally
                       931

occurring deaths will be prevented).- Approximately 50%

(170) of these prevented deaths would have resulted from
                   94/

associated renal dysfunction.-

2) A similar 60% decrease in the number of cases in the

same population is expected (i.e., 54,000 out of 90,000).

About 50% of this reduced number would be associated with
                  951

renal hypertensive changes.-

3) It is estimated that each patient with hypertensive

vascular disease suffers an average of 16 morbid days per
   961
year;-  the total for all affected patients in this

population would be 1,440,OOO morbid days (90,000 x 16).

Implementation of this program would effectively decrease

the number of morbid days by 864,000, or 60% (50% of

this number, 432,000 would involve patients with
                  971

associated renal problems).-

(2) Known Currently Non-Curable (essential) Hypertensive
   Patients:

1) It is estimated that a 15% decrease of 7,490 in mortality
                      981

from a total of 49,940 deaths- will result (27%, or

2,020, of which will have renal complications); and

2) It is estimated that a 20% reduction in the number of
                         j!J

morbid days from a base line of 25,376,OOO    will

result in 5,075,200 additional healthy days (27%, or

1,370,300 associated renal problems).


There is no change in prevalence rate or number of new

cases.

(3) Total for Known Hypertensive Patients:

   Total short-term benefits for the surveyed high-risk groups

are the prevention of 7,830 deaths (2,190 having associated

renal problems), a reduction of 54,000 cases (27,000 with

associated renal problems), and a reduced number of morbid days

by 5,939,200 (1,802,230 resulting from associated renal disease).

C.  Long-Term Benefits

  (1) Annual Long-Term Benefits

It is anticipated that the number of patients in end-stage

renal failure resulting from non-essential hypertension will be

reduced by 2,940 each year (a 60% reduction rate from an esti-
             lOO/

mated base of 4,900)-  At the same time, it is estimated that
             101/
                      -
there would be 13,880    patients suffering from essential

hypertension who would have developed end-stage uremia each year.

This number is

implementation

   The total

expected to be reduced by 104, or 1,390, by the

of this program.

annual long-term benefits will amount to a

reduction in the number of patients developing end-stage uremia

by 4,330.

(2) Cumulative Long-Term Benefits

It is felt that 7% or 98,000, m/ of all potentially curable

known hypertensives (1,400,OOO) would eventually develop chronic


renal failure.  With this program a reduction of this number by


60% (i.e., 58,800) is expected.  An additional 3.5%, or 277,550,

of the presently non-curable known hypertensives (7,930,OOO)

would eventually have developed fatal end-stage uremia.

Development of this program is designed to reduce thisfigure

            103/
by lo%, or 27,760.-

Therefore, total cumulative long-term benefits amount to

     a prevention of 86,560 cases of fatal end-stage uremia.

3.  Research

  This research program will consist of a number of problem-focussed

clinical and laboratory research studies as well as of individual grants

for wholly independent study in the pertinent areas.

The clinical research programs would be carried out in 20 separate

study groups, and laboratory research programs would also be carried out

in 20 separate study groups. 1041 Fifteen of these study groups would be

combined in the same geographic location, leaving 5 groups to accomplish

basic laboratory research independently and 5 groups to accomplish clinical

research independently.

  The laboratory research would be funded with approximately $40,000
      1051
per group, - for a total of $800,000.  The clinical research would be
                      106/

funded with approximately $50,000     per grow, or approximately

$1,000,000.  Since 15 of these groups will be concerned with both
L laboratory and clinical research, the level of support to these centers

would be $90,000 each.

  The remaining area of research would consist of approximately 50

individual grants, at $40,000 each, for a total grant cost of $2,000,000.

  The total amount for research equals $1,800,000 for laboratory and

clinical research and $2,000,000 for individual grants yielding a total


of $3,800,000 supported by HEW.  An additional $1,270,000 is expected

to be generated by other sources.

  The clinical studies mentioned above will consist of long-term stud

of the natural history and treatment of hypertensive vascular disease,

especially as it relates to renal disease.  Both the laboratory and

clinical studies will result in additional benefits to disease areas

other than renal disease such as hypertensive heart disease, arterio-

sclerosis, etc.  The basic research programs would be directed towards

the discovery of'the etiology of hypertension, the identification of

facets and factors in the disease process which affect renal function,

and the development of novel treatment methods.

4.  Training

  The training of physicians and allied personnel would cost HEW

approximately $380,000.  An additional $130,000 would be obtained from

other sources.


5.   Facilities

  The expenditures for facilities is estimated at $l,OOO,OOO with an

additional $330,000 to come from other agencies.

les

A benefit-cost summary associated with this program is found in Table

IX.


Table IX

KIDNEY DISEASES RELATED TO HYPERTENSIVE VASCULAR DISEASES, HYPOTHETICAL PROGRAM
       AT CURRENT HEW EXPENDITURE LEVEL, BASED ON THE CURRENT STATE OF THE ART

Short-Term Benefits

Long-Term Benefits

Reduction
Per Year In

Reduction In
End-Stage Uremia

Per Year

Zumulative

Expenditures

Total
($1,000)

Mortality

Prevalence

!iorbid Days

Program

5,959,200
(1,802,230;

I.A. Diagnosis and treatment of individuals
  17 years of age and over with known
  curable (non-essential) hypertension
  and non-curable hypertension
B. Supportive education and administra-
    tion

Sub-Total

II.  Research


III. Training

IV.  Facilities

TOTAL

`;;;$;$I
   3
5,330
(5,330)

4,000
(4,000)

4,000
(4,000)

412,530
(33,362)

3,800
(3,800)

  380
(380)
1,000
(1,000)

(

(4,330)

9,180
(9,180)

54,000
(27,000)

419,440    7,830
(40,272)  (2,190p

(86,560)

u  Figures in parenthesis refer to statistics attributable to renal complications.


146.

C.

Kidney Diseases Related to Hypertensive Vascular Diseases, Hypothetical
Program at Intermediate HEW Expenditure Level, Based on the Current
State of the Art

1.  Introduction

  This program has four components:
1) Screening, diagnosis, treatment, and supportive education and

administration;

2) Research;

3) Training; and

4) Facilities.

The estimated total cost for this program is $496,150,000 ($6,936,000

will be used for associated renal problems).  HEW will account for

$22,098,000 ($21,207,000 for associated renal complications). Figure

10 illustrates the total program expenditures by components. A discus-

sion of the various program components follows.

2.  Screening, Diagnosis, Treatment, and Supportive Education and
   Administration

This program is designed to cover a six-year period in order to

attain maximum effectiveness under an intermediate budget constraint.

In the intermediate program level, an additional risk group must be


considered.  This group is comprised of individuals who have not been

examined by a physician during the preceding year.  In this population,

there are an estimated 43,500,OOO persons 17 years of age and over in

     1071                        1081
the U. S.,   2,100,OOO with undiagnosed hypertension.    Over a 6 year
period, 50% (21,750,OOO) of these individuals could realistically be

screened.  This means that each year 3,792,OOO persons would be

subjected to a screening test. 1091 If only 50% of the total population at

risk is randomly screened, then it can be assumed that 50% of the

individuals with hypertension will be detected, i.e., 1,050,OOO.   Since


costs ($1,000,000)

150

100

70.0




50









21.:








I

Diagnosis and
Treatment (43.4)

!-

p!zsJTraining (.5)
         HEW
                      PROGRAM

Research (6.2)

6Training (.7)

Facilities (10.7

TOTAL

Fig. 10.  Kidney Diseases Related to Hypertensive Vascular Diseases, Hypothetical

Program Costs at Intermediate HEW Expenditure Level, Based on the
Current State of the Art.

146a


the program covers a 6 year period, 175,000 individuals will have a

positive screening test for hypertension each year.  The cost per test

is $1.25, thus, the total cost for a general screening test is

$4,740,000 ($1.25 x 3,792,OOO). $240,000 of this amount can be

attributed to renal involvement.  HEW will support 20% of the total

or $948,000 ($57,000 of which is attributed to renal disease).

   In addition to the cost of screening, expenses for treatment and

confirming diagnosis will be incurred.

  Approximately 15%, 26,500, of the 175,000 diagnosed hypertensives

are assumed to have curable hypertension.  At a cost of $1,000 per year,

total treatment and confirming diagnosis costs will be $26,250,000

($2,625,000 for associated renal complications).

  Approximately 85% (148,750) of the 175,000 have non-curable hyper-


tension.  At an estimated treatment cost of $200 per individual per

year, total costs will be $29,750,000 ($1,785,000 for associated renal

complications).  Treatment costs will be borne by sources other than


HEW.

  Total costs for this part of the program are $467,940,000

($32,726,000 for associated renal complications). HEW's share of the

total is $948,000 ($57,000 for associated renal complications).

  The supportive educational and administrative funds needed to

implement the screening, diagnosis and treatment for these hypertensive

patients is estimated to be $8,000,000 from HEW with an expected additional

$2,670,000 from other sources.  These funds are to be used for the

postgraduate education of physicians and allied medical personnel, as

well as for technical and administrative support by HEW.


The total cost for this program component is estimated to be

$478,610,000 ($43,396,000 for associated renal complications). HEW's

share is $8,948,000 ($8,057,000 for associated renal complications).

a.  Short-Term Benefits:

The following are estimated short-term benefits.

(1) Newly Detected Potentially Curable (non-essential)
   Hypertensives:

1) Of the total population of 26,250 having the disease,

140 deaths would have occurred without this program;

a reduction of 80 (60%) is anticipated (50% of which

reflect those deaths avoided in cases having asso-

ciated renal problems). 1101

2)  A 60% reduction in prevalence is also expected,

accounting for 15,750 (50% or 7,880 with associated
        1111

  renal problems).                112j
3) From a base line of 42O;OOO morbid days- a 60%

  reduction is expected, i.e., 252,000 days (126,000

in patients with associated renal problems).

(2) Newly Detected Currently Non-Curable (essential)
   Hypertensives

Short-term benefits associated with the currently non-

curable hypertensives, 17 years of age and over, are as follows:

1) An estimated 15% decrease of 160 in immediate mor-
                        1131

tality from a base line of 1,070 deaths    which would

have occurred without this program (27% of the avoided

deaths, or 40,  are attributed to cases with asso-

ciated renal problems).


2) There is no change in prevalence rate.

3) An estimated 20% reduction, 476,000, in the number
                              1141

of morbid days from a base line of 2,380,OOO

(128,520 as a result of associated renal problems).

(3) All Hypertensives

Total short-term benefits for the surveyed high-risk

groups are

1) A reduction of 8,070 deaths (2,270 with associated

renal problems);

2) A reduction in prevalence of 69,750 (34,880 with

associated renal problems); and

3) A reduction in morbid days of 6,193,72,0 (2,056,820 in

patients with associated renal problems).

b.  Long-Term Benefits

The following are estimated long-term benefits:       .

(1) Annual Long-Term Benefits

It is estimated that of a total of 550 deaths which would

have occurred in the newly detected non-essential hypertensives

annually, 60%, or 330 per year, would be prevented by this
    1151
program.

In the population with newly diagnosed essential hypertension,

a 10% reduction of 156 in the number of cases of fatal end-
                             u/

stage uremia is expected from a base line of 1,560.

Total (annual) long-term benefits for all groups surveyed

equal 4,820 prevented cases of fatal end-stage uremia each

year.


(2) Cumulative Long-Term Benefits

It is anticipated that this program will result in a

60% reduction in the number of cumulative cases of fatal

end-stage uremia in patients with newly detected non-essential

hypertension.  This would be a reduction of 6,720 from a

base line of 11,025.

1181

It is also expected that 3,120 (10% of the total 31,240)-

potential cases of fatal end-stage uremia will be prevented in

patients with essential hypertension.

Total cumulative long-term benefits for all the surveyed

high-risk groups, including those discussed above in Section

B.2.c., amount to a reduction of 96,300 cases of fatal end-

stage uremia.

3.   Research

  The research program would be expanded in the following manner:

clinical research will be expanded to include 25 separate groups at a

cost of $50,000 per group for a total of $1,250,000.

Laboratory research projects will also be expanded to include 25

separate study groups at a cost of $40,000 per group for a total of

$1,000,000.

The number of individual grants will be increased from 50 to 60

at a cost of approximately $40,000 each for a total of $2,400,000.

Total support for research efforts from HEW would amount to

$4,650,000.  An additional $1,550,000 would be generated by other

sources.

4.  Training

  The training of physicians and allied personnel will cost HEW



approximately $500,000.  An additional $170,000 would be obtained

from other sources.


5.  Facilities

HEW's expenditures for facilities is anticipated to be $8,000,000

plus an additional $2,670,000 from other sources.

A summary of the benefits and costs associated with this program is

found in Table X.


KIDNEY DISEASES RELATED TO HYPERTENSIVE VASCULAR DISEASES, HYPOTHETICAL PROGRAM
      AT INTERMEDIATE HEW EXPENDITURE LEVEL, BASED ON THE CURRENT STATE OF THE ART

Short-Term Benefits

Expenditures
     I            I

I.A. Screening, diagnosis and treatment of
  individuals 17 years of age and over
  with known curable (non-essential)
  hypertension and non-curable hyperten-
   sion and individuals who would have had
  undetected hypertension without the
   initiation of the program component     I

                                        948     4,740
    1.  Screening                     (57)   (284+
                                 -               463,200
    2.  Diagnosis and treatment                 (32,442)
                                        948   467,940
                    Sub-Total            (57)   (32,726)

                               8,000    10,670
B. Supportive education and administration    (8,000)   (10,670)

                              8,948   478,610
                   Sub-Total          (8,057)   (43,396)

                               4,650     6,200
II.  Research                      (4,650)   (6,200)
                                          500       670
III. Training                        (500)     (670)
                                8,000    10,670
IV.  Facilities                     (8,000)   (10,670)

                      TOTAL          22,098   496,150
                             (21,207)   (60,936)

8,070
(2,270)

Reduction
Per Year In

Prevalence

69,750
(34,880)

'Viorbid Days

6,193,720
(2,056,820;

Long-Term Benefits

Reduction In
End-Stage Uremia

Per Year

(4,820)

Cumulative

(95,300)

u  Figures in parenthesis refer to statistics attributable to renal complications


D.  Kidney Diseases Related to Hypertensive Vascular Diseases, Hypothetical
  Program at Accelerated HEW Expenditure Level,  Based on the Current State
   of the Art

1.  Introduction

This .program has four components:

1) Screening,. diagnosis, treatment, and supportive education and

administration;

2) Research;

3) Training; and

4) Facilities.

The estimated total cost for this program is $566,700,000 ($75,441,600

for associated renal complications).  HEW will account for $30,421,000

($28,639,000 for associated renal problems).  Figure 11 illustrates the

total program expenditures by components.  A discussion of these various

program components follows.

2.  Screening, Diagnosis., Treatment, and Supportive Education and
   Administration

With an accelerated program there is no expected change in the

target populations.

a.  Relevant Population and Program Component Costs

  The screening program for undetected hypertensive patients

will be accelerated so that rather than taking six years to reach

50% of the 43,500,OOO individuals at risk, three years would be

sufficient to complete the task.

  An average of 7,580,OOO individuals are expected to be screened
                                 1191
per year.  Of these, 350,000 will have hypertension.
Screening costs are estimated at $1.25 per individual (as part of

a general screening program).  Total screening cost is $9,480,000


costs ($1,000,000)

150

100

75.4

50

28.6

[Research (5.5)
ITrain

-ng

Facilities
(11.6)  I

(1.4)

Diagnosis
  and
Treatment
(50.7j

Research (7.3)

Facilities
(15.5)

HEW

PROGRAM

TOTAL

Training (1.9)

Fig. 11.  Kidney Diseases Related to Hypertensive Vascular Disease,
     Hypothetical Program Costs at Accelerated HEW Expediture Level,
      Based on the Current State of the Art.

152a


353

per year ($569,000 attributed to associated renal problems). HEW
will contribute to this program an estimated $1,896,000 ($114,000

for associated renal problems).

  If 15% of the 350,000 patients with positive screening tests

have curable hypertension (i.e., 52,500 and if the yearly treat-

ment and confirming diagnosis cost per individual is $1,000, then
total treatment costs for this group are $52,500,000 per year
(10% or $5,250,000 for associated renal complications).
  If 85% of the 350,000 have currently non-curable hypertension

(i.e., 297,500), and if the estimated cost of treatment is $200 per

individual per year,  total treatment costs .for these individuals

are estimated at $59,500,000 per year ($3,570,000 for associated

renal disease).

  Total costs for this component (and for all the surveyed popu-
lation) is now estimated at $528,680,000 ($37,421,000 for associated

renal complications).  HEW's contribution is $1,896,000 ($114,000

for associated renal disease).

  Financial support for education and administration in the

accelerated program is $10,000,000 to come from HEW with an additional

$3,330,000 anticipated from outside sources.

  The total cost for this program component is $542,010,000

($50,751,000 for associated renal complications), of which HEW will

contribute $11,896,000 ($10,114,000 for associated renal complica-

tions).

b.  Short-Term Benefits

The following are estimated short-term .benef its


(1) Newly Detected Potentially Curable (non-essential)
   Hypertensives:

1) A 60% decrease in the immediate mortality of the in-

dividuals with curable hypertension is anticipated.
Prom a base line of 2gp'deaths occurring without

this health program, there would be 170 prevented

deaths (50% or approximately 90 reflect deaths avoided

in patients having associated renal problems).

2) A 60% reduction in prevalence of 31,500 from the base

line of 52,500 cases is expected (50%, or 15,750,
                  1211

  with associated renal problems).

3) Morbid days are also expected to be reduced by 60%

from a base line of     &zJ/
             840,000   to 504,000 (252,000

attributed to associated renal disease).

(2) Newly Detected Currently Non-Curable (essential)
   Hypertensives:

1) An estimated 15% decrease in mortality from a base
           1231

  line of 2,14U deaths to 320 (27% or 90 patients

  having associated renal disease).

2) An estimated 20% reduction in the number of morbid

days is anticipated, i.e., a decrease of 952,000
                   1241
from a base line of 4,760,OOO - (27% or 257,040 due

to associated renal problems).

(3) All Surveyed Hypertensives:

  Total short-term benefits for the surveyed high-risk groups

are 10,260 prevented deaths (2,370 with associated renal prob-

lems), a reduction in the number of cases by 85,500 (42,750

with associated renal problems), and a reduction in morbid days


     by 7,395,200 (2,311,340 in patients with associated renal

     problems).



     C.  Long-Term Eenefits

     The following are estimated long-term benefits:

     (1) Annual Long-Term Benefits

        Under an accelerated program, there will be no change in

     the number of currently undiagnosed hypertensives who can be

     reached compared to the number reached in the intermediate


       program.  Therefore, the annual long-term benefits will be

     identical with that group:  an annual reduction of fatal end-

     stage uremia by 330 in currently non-curable hypertensives.

        Total annual long-term benefits for all the surveyed high

     risk groups equal a reduction in fatal end-stage renal failure

     by 4,820 each year.

     (2) Cumulative Long-Term Benefits

        No changes from the intermediate program are anticipated.

     A reduction of 3,120 in the number of cases of fatal end-stage

       uremia will occur.

        Total cumulative long-term benefits for all of the surveyed

     high-risk groups are 96,300 prevented cases of fatal end-stage


        uremia.


3.   Research

  Under an.accelerated HEW funding program, an additional increase fn

the number of research projects is anticipated to encompass a total of

30 laboratory I esearch study groups costing $40,000 per group, for a

total cost of $1,200,000.  Thirty clinical research study groups costing

$50,000 per group will also be in progress yielding a total of $1,500,000.


Approximately $2,800,000 will be expended on 70 individual research

grants, averaging $40,000 per grant.  Total HEW support for research is

               An additional $1,830,000 is anticipated

expected to be $5,500,000.


from outside sources.


4.  Training

  The training of physic

ians and allied medical personnel wou Id cost

HEW approximately $1,425,000 with an additional $475,000 from other



sources.


5.   Facilities

  Under an accelerated HEW health program, $11,600,000 would be

expended on facilities.  An additional $3,860,000 would come from other



sources.

A summary of the benefits and costs associated with this program is

Found in Table XI.


Table XI

KlDNEY DISEASES RELATED TO HYPERTENSIVE VASCULAR DISEASES, HYPOTHETICAL PROGRAM
       AT ACCELERATED HEW EXPENDITURE LEVEL, BASED ON THE CURRENT STATE OF THE ART

Program

          ----___---- I--
I__-.__--_-----._                 -.
1.A. SC~CCILLII~, diagnusis and treatment of
   individuals 17 years of age and over
   wit11 lalown curable jnou-esse,ltial) hy-
   pertension and non-curable hypertension
    and individuals who would have had uu-
   detected Ilypertension without the ini-
   tiatiolr of the program component.

1.  Screening

2.  Diagllo+is and treatment

B. Education and administration for I.A.

Sub-Tota

11,896   542,010
(10,114)   (50,751)

II.   Research                         5,500     7,330

III. Training                         1,425     1,900

IV.   Facilities                       11,600    15,460

TOTAL

      Short-Term Benefits
r---

Expenditures   I

Reduction
Per Year In

    -
(Sly&
      -

1,896
(114)

1,896
(114)

10,000
(10,000)

30,421   566,700    10,260
(28,639   (75,441)    (2,380)
--~  -

Total
($l.,OOO)   Mortality
              .-

519,200
(36,852)
528,680
/97 1.9,

Prevalence

---
85,500
(42,750)

!lorbid Days
-          -

Long-Term Benefits

Cumulative

   Reduction in
End-Stage Uremia
---

Per Year
.---.

:4,820)   (96,300)

11  Figurts in parenthesis refer to statistics attributable to renal complications.


E.  Kidney Diseases Related to Hypertensive Vascular Diseases, Hypothetical
  Program for Fiscal Year 1975, at Accelerated HEW Expenditure Level,
  Based on the Expected Advanced State of the Art in 1975

1.   Introduction

  This program has four components:

1) Screening, diagnosis, treatment and supportive education and

administration;

2) Research;

3) Training; and

  4)   Facilities.

  The estimated total cost for this program is S878,675,000

(5101,438,OOO for associated renal problems). HEW will account for

$37,899,000 ($35,832,000 for associated renal problems).

Anticipated advances in the state of the art include:

1) Advances in the knowledge concerning the underlying caus:es of

hypertension, e.g., an appreciation of the renin-angiotensin

mechanism;

2)  Specific therapy directed toward the underlying causes of hyper-

tension, e.g., an anti-renin substance in a situation in. which

renin could be a cause of hypertension;

3)  Improved diagnostic tests for detecting hypertension, e.g.,

advanced use of radio-isotopes,  improved split renal function

tests, implementation of photo-electric methods for determining

high blood pressure, etc.; and

4) Advances in the art of treatment of surgically treatable hyper-

tension, e.g., improved vascular prostheses, etc.

Figure 12 illustrates the total program expeditures by components


costs ($1,000,000)

150

101.4

50

35.8

Facilities

HEW

PROGRAX

r

Diagnosis &
Treatment
  (70)

Research
(12.0)

Training (4.0)

Facilities
(15.&j

TOTAL

Fig. 12.  Kidney Diseases Related to Hypertensive Vascular Diseases,
     Hypothetical Program Costs for Fiscal Year 1975, at
     Accelerated HEI? Expenditur'e Level, Based on Expected
       Advanced State =f the Art in 1975.

157a


358

including associated renal disease.  A detailed discussion of the various

program components follows.

2.  Screening. Diagnosis. Treatment, and Supportive Education and
   Administration

In 1975, the accelerated program activity reflects changes in the

population.  The ratio of the 1975 population of individuals 17 years of
                                1251

age and over to that of 1966 is estimated at 1.16.    No changes in the

number of target population groups are anticipated.


    a.  Relevant Population and Program Component Costs

    It is estimated that there will be about 104,400 patients with

non-essential hypertension from among currently known hypertensives

receiving more adequate treatment.  At an estimated cost of $1,000

per individual treated per year, a cost figure of $104,4OO,OC~O (lo%,

or $10,440,000, for those having associated renal disease) is arrived

at.

In 1975, there will be approximately 9,198,800 individuals with

essential hypertension among those currently knomto be hypertensives.

This accelerated program is designed to affect 20% of these individuals.

As a result of improved treatment programs and further advances in

the state of the art, it is estimated that the treatment costs for

                     $300. 1261
these individuals per year is        Assuming no additional expense

for screening, the cost for treatment and differential diagnosis for

the affected individuals is now estimated at $551,928,000 (6%, or

$31,116,000, attributed to associated renal problems).

  In 1975, assuming no change in the current health services

system, there will be 50,460,OOO individuals 17 years of age and

over who have not been seen by a physician in the previous ytear.


Again, it is assumed that the program will be able to reach 50%

of these patients (26,390,OOO) over a three-year period.  With an

accelerated program effort, approximately 3.3% (8,797,440) of these

persons will be reached each year,  Screening costs per individual

per year remain at $1.25 (as part of a general screening program).

The total cost for screening is estimated at $10,997,000 ($660,000
                      1271
for associated renai dysfunction).    HEW's share in this program

is estimated to be $2,199,000 ($132,000 for associated renal disease).

  Of the anticipated 2,436,OOO individuals who will have hyper-

tension detectable in these screening tests, it is assumed that 50%

will be detected over a period of three years; 406,000 will be

reached each year.  Of this group, 15% or 60,900 individuals will

have non-essential hypertension.  At a cost of $1,000 per year per

individual for treatment and differential diagnosis, the total cost

in this group is $60,900,000 (10% or $6,090,,000 for patients with

associated renal problems).

  Approximately 85% of the 406,000 hypertensive patients, or 345,100,

will have essential hypertension.  At a cost of $300 per year per

individual for treatment,  the total cost is estimated to be

$103,530,000 (6%. or $6,212,000, attributed to associated renal

diseases).

  Total treatment costs for all groups are estimated at $820,758,000

($53,858,000 for associated renal problems).   These costs are not

expected to be borne by HEW.

  Total cost for this entire component (screening, diagnosis, and

treatment) is $831,755,000 ($54,518,000 for associated renal problems).


HEW will contribute $2,199,000 ($132,000 for associated renal

problems).

  The educational and administrative support for this program

component is estimated to cost $15,460,000 of which $11,600,000

would come from HEW and an anticipated $3,860,000 would come from

other sources.

  Total cost for the entire program component is $847,215,000

(S69,978,000 for associated renal problems).  HEW's contribution

is $13,799,000 ($11,732,000 for associated renal problems).
             s/
b.  Short-Term Benefits

  The following are estimated short-term benefits:

(1) Known Hypertensives with Potentially Curable (non-essential)
   Hypertension:

1) A 65% reduction in immediate mortality is expected from a

  base line of 660 expected deaths (i.e., 430 prevented

  deaths of which 220 have associated renal problems).

  About 5 of the 65%, or 30 (20 from renal involvement),

  can be attributed to the advanced state of the art;
2) A reduction of 65% in prevalence is anticipated, or

  67,860, from a base line of 104,400 (33,930 with renal

  problems).  About 5 of the 65% or 5,220 prevented cases

  can be attributed to advances in the state of the art

  (2,610 with renal problems); and

3) A 65% reduction in the number of morbid days from a

base line of 1,670,400, or a reduction of 1,085,760 days

  (542,880 of the reduction in morbid days would have

  associated renal problems).  About 5 of the 65% reduction

  in morbid days, or 83,520, is attributed to advances in


the state of the art (41,760 are in patients with renal

problems).

(2) Known Hypertensives with Essential Hypertension

  1) Mortality will be reduced by 55%, or by 31,860, from a

    base line of 57,930 (8,600 with associated renal problems).

     Forty of the 55% decrease, or 23,170, is attributed to

    advances in the state of the art (6,260 represent patients

     with associated renal problems);

   2)  It is estimated that a 40% reduction of 735,900 in the

    number cf cases from a base line of 1,133,760 will occur

     (198,690 with renal complications) all of which is attribu-

     ted to advances in the state of the art; and

  3) A 50% reduction in morbid days, or 14,718,050, is

     anticipated from a base line of 29,436,160 (3,973,880

     in patients with associated renal problems).  Thirty of

     the 50% reduction, or 8,830,850 days are attributed to

     the advances in the state of the art (2,384,330 in

     patients with associated renal disease).

(3) Undiagnosed Individuals with Non-Essential Hypertension

  1) An estimated reduction in immediate mortality by 65%, or

     by 220,  from a base line of 340 (110 with associated renal

     problems).  About 5 of the 65% reduction, or 20, is

     attributed to advances in the state of the art (10

     represent patients with associated renal problems);

  2) A 65% reduction, 39,590, in prevalence is also anticipated


  from a base line of 60,900 (19,800 are patients with

  associated renal problems).  About 5 of the 65%

  reduction, or 3,050 controlled cases are attributable

  to advances in the state of the art (1,530 of these

  would have had associated renal problems); and

3) Morbid days will be reduced by 65%, or 633,360, from a

  base line of 974,400 (316,680 of these in patients with

  associated renal problems).  Five of the 65% reduction,

  or 48,720 days are attributable to advances in the

  state of the art (24,360 in patients with associated

  renal problems).

(4) Undiagnosed Individuals with Essential Hypertension

  1) A 55% reduction in immediate mortality, or 1,360, is

    anticipated from a base line of 2,480 deaths (370 of the

    prevented deaths would have been associated with renal

  failure).  Forty of the 55% reduction, or 990 deaths

  avoided are attributed to advances in the state of

  the art (270 in patients with associated renal problems);

2) Prevalence will decrease by 40%, or by 138,040, cases,

  from a base line of 345,100 (37,270 would be cases

  with associated renal disorders) all of which is

  attributable to advances in the state of the art; and

3) A 50% reduction in morbid days, or 2,760,800, is

anticipated from a base line of 5,521,600 (745,420 in

patients with associated renal problems).  Thirty of the

50% reduction, or 1,656,480 morbid days avoided may be

attributed to advances in the state of the art (447,250


363

   of these in patients with associated renal disease).

(5) All Surveyed Hypertensive Patients

  1) Immediate mortality will be reduced by 33,870 cases

    (9,300 would have been patients with associated renal

     problems).  Approximately 24,210 of these are attributed

    to advances in the state of the art (6,560 of these

would have been patients with associated renal problems);

2) Prevalence will be reduced by 981,390 cases (289,690

with associated renal problems).  882,210 of the total

reduction in prevalence is attributed to advances in the

state of the art (240,100 would have been patients with

associated renal problems); and

3) Morbid days will be reduced by 19,198,OOO (5,578,860 in
patients with associated renal problems).  Approximately

  10,619,570 of the total reduction is attributed to

  advances in the state of the art (2,897,700 in patients

with associated renal problems).

           1291
C.  Long-Term Benefits

(1) Annual Long-Term Benefits

It is anticipated that 3,690 out of 5,680 individuals with

known non-essential hypertension (who would normally progress

to renal failure), can be prevented from developing end-stage

kidney failure each year.  Approximately 5 of this 65% reduction
(a reduction of 280 cases/year) is attributed to advances in the

state of the art.


  For the group of known patients with essential hypertension,

it is expected that 4,830, or 30% of 16,100 individuals (who

would develop renal failure), can be prevented from progressing

to end-stage renal failure each year.  About 20 of the 30%

reduction (a reduction of 3,220 cases/year is attributed to

advances in the state of the art.

  In the group of individuals with undetected non-essential

hypertension it is anticipated that a 65% reduction in end-
stage uremia will occur from the base line of 640 (420 such

cases averted each year).  About 5 of the 65% reduction, or

30 cases of prevented end-stage uremia per year are attributed

to advances in the state of the art.

  In the group of individuals with undetected essential
hypertension it is anticipated that a 30% reduction (540 cases)

in end-stage uremia will occur from a base line of 1,810 cases

of renal failure which would normally occur each year.  About

20 of the 30% reduction, or 360 cases averted can be attributed

to advances in the state of the art.

  For all surveyed hypertensive groups the reduction in end-

stage uremia is estimated at 9,480 per year.  Approximately

3,890 of these cases are attributed to advances in the state

of the art.

(2) Cumulative Long-Term Benefits

  In the group of patients with known non-essential hypertension

a 65% reduction in cumulative long-term cases of end-stage uremia

is anticipated.  This will amount to a reduction of 73,890


cases from a base line oi 113,680.  Approximately 5 of the 65%

reduction, or a reduction of 5,680 cases of end-stage uremia

can be attributed to advances in the state of the art.

  In the group of patients with known essential hypertension

a 30% reduction in cumulative long-term end-stage uremia is

anticipated.  This amounts to 96,590 cases avoided from a

base line of 321,960.  About 20 of the 30% reduction, or 64,390

cases of end-stage uremia avoided, are attributed to advances

in the state of the art.

   In the group of individuals with undetected non-essential

hypertension it is estimated that a 65% reduction in end-stage

uremia will occur.  This will amount to 8,310 cases avoided

from a base line of 12,790 (5 of the 6.5% reduction, or a reduc-

tion of 640 cases,  is attributed to advances in the state of the

art).

   In the group of individuals with undetected essential hyper-

tension it is anticipated that a 30% reduction of 10,870 in

the number of cases of end-stage uremia will occur from a

base line of 36,240.  About 20 of the 30% reduction, or a

reduction of 7,250 cases is attributed to advances in the

state of the art.

  Total cumulative long-term benefits for all groups surveyed

are the prevention of 189,660 cases of end-stage uremia, 77,960

of which are attributable to advances in the state of the art.

3.  Research

  It is anticipated that in this hypothetical situation an estimated

$9,500,000 would be required from HEW and an additional $2,500,000 from


other institutions to support the various research programs.

4.  Training

  With the advanced state of the art, it is anticipated that there

will be an additional requirement for the training of physicians and
allied medical personnel requiring increased financial support amounting
to $3,000,000 from HEW with an additional $l,OOO,OOO to come from other

agencies.

5.  Facilities

Expenditures for facilities are estimated to be $15,460,000 of which

$11,600,000 will come

from other sources.

from HEW and an additional $3,860,000 will come

A benefit-cost summary associated with this program is presented in

ible XII.

6.                                      1301
  Estimated Benefits Dependent on Research and Development

  Advances in the state of the art would produce a further 5% decrease

in short-term mortality, prevalence, and morbid days for known patients

with non-essential hypertension.  A 5% long-term reduction in end-stage

uremia is also anticipated.

  A further 40% decrease in immediate mortality and prevalence is

estimated for the group of patients with known essential hypertension.

Also anticipated is an additional 30% decrease in morbid days and an

additional 20% reduction in end-stage renal failure.

  A summary of the short-term benefits dependent on research and

development follows:


Table XII

KIDNEY DISEASES RELATED TO HYPERTENSIVE VASCULAR DISEASES, HYPOTHETICAL PROGRAM FOR FISCAL YEAR 1975
  AT ACCELERATED HEW EXPENDITURE LEVEL, BASED ON EXPECTED ADVANCED STATE OF THE ART IN 1975

                                                        Short-Term Benefits       Long-Term Benefits


                                                                   Reduction              Reduction In
                              Expenditures               Per Year In         End-Stage Uremia

                                         HEW      Total
           Program              ($1,000)   ($1,000)  Mortality Prevalence Morbid Days  Per Year Cumulative

I.A. Screening, Diagnosis and treatment of
   individuals 17 years of age and over
  with known curable (non-essential)
  hypertension and non-curable hyperten-
   sion and individuals who would have
  had undetected hypertension without the
  initiation of the program component      2,199
    1.  Screening               (132)Li , 10,997
                                       (660)

                                    820,758
    2.  Diagnosis and treatment                 (53,858)

                                 2,199   831,755
                    S,~b-'rntnl
                            ----_           (132)   (54,518)

                                11,600    15,460
B. Supportive education and administiation   (11,600)   (15,460)

                                 13,799   847,215
                   Sub-Total         (11,73Y)   (69,978)

                                 9,500    12,000
II.   Research                      (9,500)   (12,000)
                                 3,000     4,000
III. Training                      (3,000)   (4,000)
                                11,600    15,460
IV.   Facilities                     (11,600)   (15,460)
    j (::$z) (:(:;;:;;) ;;$:) (,","::,',":)
                       TOTAL            Is::Y:r,"k':,( (9,480) / (189,660)
Ll   Figures  in nni-,'t~i :~cac,i';  1-1, f,, ,-  +,> ctq,;..~:     ,.. :'


1) 24,210 prevented deaths (6,560 in patients with associated renal

  problems);

2) A reduction in prevalence by 882,210 (240,100 cases with

  associated renal problems); and

3) A reduction in morbid days by 10,619,570 (2,897,700 in patients

  with renal problems).

A summary of the long-term benefits includes:

1) An annual reduction in cases of end-stage kidney disease of

  3,890; and

2) A cumulative reduction in the cases of end-stage kidney disease

  of approximately 77,960.

   All of these benefits have been based on the projected 1975 population

of individuals 17 years of age and over, which is estimated to be 16%

greater than the 1966 population.  Disregarding the effects of population

changes, it is estimated that the following short-term benefits are the

result of research and development advances (using 1966 population figures):

  1) Approximately 20,870 prevented deaths (5,660 in patients with

     associated renal problems);

2) A reduction in prevalence by 760,530 (206,980 cases with associated

  renal problems); and

3)  A reduction in morbid days by 9,154,800 (2,498,020 in patients

     with associated renal problems).

  Long-term benefits dependent on research and development are estimated


as follows:

1) An annual reduction in the cases of end-stage kidney disease of

  3,350; and

2) A cumulative reduction in the cases of end-stage kidney disease of

67,210.


               V.  END-STAGE KIDNEY DISEASE


A.  Introduction

  This section describes programs which are concerned with alleviating the

effects of end-stage kidney disease-- the result of a natural progression of

the infectious, hypersensitivity, hypertensive, and other kidney disease


processes.  End-stage kidney disease is currently treated by two procedures,

chronic intermittent hemodialysis and kidney transplantation.
                                 1311
  Approximately 50,000 people die as a result of uremia each year.-

Of these 50,000 about 79$ are in the age group above 55, about 1% are in

the age group 15-54, and about 2$ are in the age group O-14. It has been
                                    132/
estimated that of the 50,000 annual end-stage uremia victims, about 8,00-

are ideally suited for dialysis therapy.  While published estimates of

transplant candidates are not available, it is assumed for the purposes of

this report that about 6,000 of the ideal dialysis candidates are.also ideal

transplant candidates.  It is also assumed that an additional 2,000 persons
                                1331
would be suited for transplantation but not for chronic dialysis.-  Most

patients suitable for either procedure are within the 15-54 age group.

  A schematic representing the progression of a patient into a hemodialysis
and/or transplant program is presented in Figure 13. With the development of

end-stage uremia, the patient becomes a candidate for chronic intermittent

dialysis or renal transplantation.  Following the transplant procedure

(especially if a cadaver kidney has been used), the patient may require

temporary dialysis until the transplanted kidney is functioning normally.

If the transplant has been successful, the patient exits from the program.

If the transplant is unsuccessful, the patient is returned to the chronic


\

Infections cf    Hypertensive    Hypersensitivity
the Kidney     Kidney Disease     Kidney Disease

Other Kidney or
Urinary System

End-Stage Uremia

Chronic

Intermittent
Dialysis

Transplantation I-

i                               \

/

unsuccessful
transplant

Fig. 13.  Schematic of Transplant and Dialysis Patients.

168a


intermittent dialysis program either for life or to await a second attempt

of transplantation.  Certain patients undergoing chronic intermittent

dialysis therapy are suitable for transplantation and may be dialysed

only until a matching donor kidney is available.  Death, of course, can

occur at any stage in the schematic.

  Benefits attributable to the various dialysis programs presented in this

section are measured in terms of reduction in mortality (lives prolonged) for

the year in which the program is active.

  In contrast to transplantation, which--if successful--is a one-time

treatment, chronic dialysis is an ongoing type of treatment.. All patients

on dialysis who survive the first year must be treated in successive years.

Thus, if during year x, there are 1,000 patients who are being maintained

on hemodialysis, all of these patients less those dying during the year

must be treated in subsequent years.  If the mortality rate among these

1,000 dialysis patients is 20$, only facilities for some 200 new patients

would be available for the 8,000 ideal dialysis candidates who will develop

end-stage uremia during the next year.  This situation is further compli-

cated by the addition of those persons with unsuccessful transplants who

require subsequently chronic dialysis treatment in order to survive.

  The benefits attributed to transplantation are measured in terms of a

reduction in mortality (patients cured).  As is shown in Figure 14, the
patient undergoing transplantation a~, a~ a resu:lt of the procedure, a) be

cured, b) die, or c) have an unsuccessful transplant subsequently he will

enter a chronic dialysis program or be retransplanted. The benefits, as

measured here take into account only those who are cured by the transplant

procedure.  Those persons not successfully transplanted who survive will,

of course, become part of the chronic dialysis patient population or will

be retransplanted.


Four specific programs have been postulated in this analysis. (See
Chapter 4, Research Methodology.) These are described in detail in the

following sections.

B.  End-Stage Uremia Program, Hypothetical Program at Current HEW Expenditure
  Level, Based on Current State of the Art

1.  Introduction

This program has five components consisting of:
1) Treatment by dialysis,
2) Treatment by transplantation,
3) Research,
4) Training, and
  5) Facilities.

HEW costs and total costs of this program sre presented in Figure 14.

As can be seen, total program costs are about $33,000,000 with H&
expenditures at approximately $21,000,000.  This hypothetical program is

essentially a reflection of the current allocation of funds for end-stage

uremia programs.  A discussion of the various components of the program

follows.

2.  Dialysis Treatment
As was indicated earlier, with the present operational state, only
about 8,000 of the 50,000 annual uremic victims are ideal candidates for

life-long chronic hemodialysis. Of these 8,000 annual dialysis candi-
       134/

dates about 75+ are currently receiving treatment. Treatment costs
                                   135/
for some 225 of these treated patients can be attributed to HEW funding,-
                    136/
about 175, to the Veterans Administration  and the remainder to other



sources.


costs ($1,000,000>

150

100

50

32.!

20.;

,

                *           Treatment (17.8)
Treatment (7.2)

Research (12.1)            Research (12.8)
            Training (1.0
J        4lFatzilic'ec (0                (l-3)

HEW

PROGRAM

TOTAL

Fig. 14. End-Stage Uremia, Ky-pothetical Program Costs at Current HE%
   Expenditure Level, Based on the Current State of the tit.

170a


  The present cost of chronic dialysis is approximately $15,000 per
        137/
year per patient.-  The cost of dialysis as used here is derived from

the cost in organized hospital dialysis centers supported by Government

funds.  If such a treatment were to be undertaken independently, private

costs would run considerably higher.  It has been estimated for the

purposes of this study that the cost of private dialysis is on the order

of $20,000 per year per patient.  Current total expenditures for chronic

dialysis therapy for the year are approximately $13,000,000 of which
                    138/
about $3,400,000 can be attributed to HEW.-.

  In determining the benefits associated with this dialysis progrsm,

(see Section A above), it is assumed that treated patients, suffer an
              139/
annual 20$ overall mortality.-  Approximately 600 lives are saved

due to the total current program efforts. Of these, about 180 lives

saved can be attributed to HEN funding.

3.  Transplantation Treatment

  As indicated above, approximately 8,000 individuals of the 50,000

who die annually from end-stage uremia are ideally suited for trans-

plantation.  Of these, approximately 300 patients per year are now being

treated by transplantation.  About 240 of these can be attributed to
      1401
HEW funding.-  Those individuals who are not cured by transplantation

and who survive, usually must revert to chronic intermittent dialysis in

order to survive.

The cost of transplantation is estimated to be. approximately $16,000
        1411

per patient per year.-  A total of $4,800,000 is spent in transplant
                             142/
treatments of which about $3,800,000 can be attributed to HEW.-


  Benefits associated with this transplant progsem are measured in
terms of a reduction in mortality (patients cured, see Section A above).
me average mortauty rate among patients -d-going trs-pls.ntation
(with kidneys from living donors or UtitiZiw I'Cadaver kidneW") is
            143/
estimated to be about 40$.-  Among the 6~$ who survive, about one-half
     144/
are cured.-  The remainder must revert to chronic hemodialys3.s

therapy or adjunctive dialysis pending retrensplentation. The number

of patients cured as a result of the total program was found to be

90 of which 72 can be attributed to HEW funding.

4. Research

  Expenditures in dialysis and transplant research totaled about

$l2,800,000 of which $L2,100,000 was expended by HEW. Current HEN

programs include intra- and extramural laboratory and ellnical research
                       142/
and demonstration grants involving about 188 projects.-

5.  Training
  It-is estimated that about $l,OOO,OOO is being expended by HEN in

the area of trdning and education of personnel to work in dialysis and

transplant operations and related research programs.  This value also
                     146/
reflects total U. S. traLning expenditures.-

6. Facilities

Expenditures for facility construction, expansion and remodeung
                 147/
are estimated to be about $1,300,000,-  of which $~oO,OOO is being

expended by HEM.

No benefits were estimated for research, training and faciYtY expend-
itures although quite obviously these funds will provide long-term

benefits.


`73

7. Summary

HEN expenditures for this program are about $21,000,000 with total

program expenditures estimated at about $33,000,000. Total benefits

derived from these expenditures are about 690 lives saved of which

about 250 can be attributed to HEW.

A summary of benefits and costs attributed to this program are presented

in Table XIII.


Table XIII

   END-STAGE UREMIA, HYPOTHETICAL PROGRAM
AT CURRENT HEW EXPENDITURE LEVEL, BASED ON THE CURRENT STATE OF THE ART

Programs

Dialysis

Transplant


Research

Training

Facilities

Totals

     Expenditures
(f ywooo)     Total
       ($ 1,000)

3,400     13,025

3,840     4,800

12,100     12,800

1,000      1,000

  500     1,300


20,840     32,925

Short-Term Benefits

Reduction in Mortality for 1966

HEW Program
(No. of Lives)

180

72

252          690

Total Program
(No. of Lives)



    600

    90,


I. End-Stage Uremia, Hypothetical Program at Intermediate HEM
Expenditure Level, Based on Current State of the Art

1.  Introduction

This program describes what could be accomplished in an end-stage
uremia program tith an "intermediate" funding level (i.e., two to
three times greater than the current level), and no change in the

current state of the art.  There are five components inthis program

including:

1) Dialysis treatment,

2) Transplantation treatment,

3) Research,

4) Training, and

5) Facilities.

  The total cost of-this intermediate program would be about

$70,500,000 of which HEW would contribute about $56,000,000. Figure 15

graphically presents the expenditures under this program. A description

of the program components follows.

2.  Dialysis Treatment

  There are now a total of 1,430 persons undergoing chronic dialysis

therapy due to the increase in fundssupporting treatment. Of these,

about 880 can be attributed to HEM support. It is estimated that

because of the general availability of HEN funds,  the VA will have about

200 chronic dialysis patients (an increase of 25 over the current level

program), and that there will still be about 350 patients being treated

through other resources.

It is anticipated that the annual cost of chronic dialysis till-

.remaLn at about $15,000 per year for patients supported -by HEW and VA

funds, and that treatment by private resources will remain at about

$20,000.  A total of $21,000,000 will be expended for dialysis treatment.


150

100









70.5






56
50

Treatment

(30)

Research

(18)

Training (5.5)
!zaclLltles (L.3,

   HEY

PROGRAM

Treatment

(43)

Research
(18.7)

Training (5.5)
Facilities (3.3)

    TOTAL

Fig. 15. End-Stage Uremia, Hypothetical Program Cos,ts at Intermediate.
    HEW Expenditure Level, Based on the Current State of the Art.

174a


I.75

It is assumed that there is no change in the 2$ annual overall
mortality rate associated with chronic dialysis therapy. Total
benefits derived from this program are about 1,144 lives prolonged
of which about 704 can be attributed to HEN funding.

3. Transplant Treatment

This program provides financial support for 1,387 persons undergoing

kidney transplantations on an annual basis. Of these, about 1,187 can

be attributed to HEN funding.  It is assumed that the cost of trans-

Plantation will remain at $16,000, which as indicated previously,

includes the actual transplant procedure and pre- end post-operative

supportive therapy.  The total cost of the trtisplant program is about

$22,200,000 of which HEW contributes about $19,000,000.

The benefits associated with this program sre measured in terms of

a reduction in mortality (patients cured). It is assumed that the

general increase in funding has not markedly affected either the
mortality rate associated with this procedure (about 46) or the cure
rate among surviving transplantees (about 50$). About 416 patients
are cured as a result of this program of which 356 can be attributed

to I-E% funding.

4. Research

It is anticipated that research expenditures will increase to about
$1R,000,000.  While no specific research plans for dialysis and trans-

Plantation will be outlined, it is anticipated that the existing 188
intra- and extramural research projects (please see previous program)
till increase in number and in some instances, in scope. Research



3.76

efforts to reduce the costs of chronic dialysis therapy and to improve
immunosuppression and organ matching techniques ~I.11 be intensified.
It is estimated that an additional $700,000 will be expended by
voluntary health agencies in dialysis and transplant research.

5.  Training
HE!W training expenditures for basic and on-the-Job education for

staff to work in dialysis and transplant therapy will increase to about

$5,500,000 to measure up to the additional needs. No other expenditures

in this area are anticipated from outside sources.

6. Facilities

HEW facility expenditures are expected to increase to about

$2,500,000 with outside funding estimated to be about $800,000. This

increase reflects the need for additional facilities for treatment of

end-stage uremia patients.

  HEW expenditures for this program are estimated to be about
$56,000,000 with total program expenditures estimated at about

$71,000,000.  Total benefits in terms of reduction in mortality derived
from the program are about 1,560 lives of which 1,060 can be attributed

to HEW funding.

A summary of the benefits and costs of this program is presented in

Table XIV.


Table XIV

    END-STAGE UREMIA, HYPOTHETICAL PROGRAM
AT INTERMEDIATE HEW EXPENDITURE LEVEL, BASED ON THE CURRENT STATE OF THJZ ART

Short-Term Benefits

                 Expenditures       Reduction in Mortality for 1966

                          Total        HEW Program    Total Program
    Program   ($ Ew    ($ l.,OW      (No. of Lives) (No. of Lives)

Dialysis         11,000      21,000             704         1,144
Transplant       19,000      22,200             356            416

Research         18,000      18,700
Training         5,500      5,500
.
Facilities        2,500       3,300

               56,000      70,700          1,060         1,560


D.  End-Stage Uremia, Ry-pothetical Program at an Accelerated m
Expenditure Level, Based on Current State of' the Art


   1.  Introduction

    This program describes what could be accomplished in an end-stage

  uremia program with a funding level about 10 times that of the current

  program and with no changes in the state of the art, that is, assuming

  no significant technological or research advanCeSo  There are five

  program couponents including:

    1) Dialysis treatment;

    2) Transplantation treatment;

    3) Research;

    4) Training; and

    5) Facilities.

The costs of this accelerated HEW program will be approximately ten

times the cost of the current program, or.about $210,000,000.  Total

program costs till be approximately $23O,OOO,OOO and t&e into account

expenditures by other federal agencies and the private sector of the


economy.  Figure 16 graphically presents the costs of the accelerated

kidney disease program assting the current state of the art.  Based

on the nature of the two specific types of treatment, their results,

the nature of the patient population available, and time and facility

requirements, the assumption is made that about 30$ of the patients
will be treated by chronic dialysis therapy and the remainder by a

transplant-dialysis therapy program.  Descriptions of specific components

of the total program and their associated benefits follow.


:  3 ($l,OOO,OOO)

-









-





-

Treatment

(171)

Research
(24)

  Training
    (10)
Facilities (5)

HEW

PROGRAM

Treatment

(199)

Research

(24.2)

Training
(10)

lacilities (5.8)

TOTAL

Fig. 16.  End-Stage Uremia, Hypothetical Program Costs at Accelerated
    HEN Expenditure Level, Based on the Current State of the Art.

177a


2.  Dialysis Program

  A total of about 5,100 patients will undergo chronic dialysis

therapy; 4,500 of these can be attributed to HEW funding. It is

estimated that the Veterans Administration is now treating about 225

patients and that the cost of 350 patients is borne by private and

other sources.

  Under the circumstances of greater efficiency associated with mass
treatment, it Is assumed that dialysis costs have decreased to $10,000

per year per patient.  HJ3W expenditures for dialysis treatment total

approximately $45,000,000.  As indicated above, it is assumed that

because of the availability of HEW money, private and VA funding for

dialysis will not change materially.  The total costs for dialysis

treatment are now estimated at approximately $55,000,000.

  It is assumed that the overall annual mortality of 20$ among d%alysis

patients has not changed.  Applying this mortality factor to the patients
undergoing therapy, it can be surmised that 3,600 lives will be

prolonged by HEN funds.  The benefits associated with the total program
are about 4,100 lives prolonged.  As indicated previously, these
benefits are anticipated during the first year the program is in effect.

3.  Transplant Program

Because of the availabiU.ty of funds about 11,000 patients will now

be treated on an annual basis.  Of these, approximately 10,500 are
attributed to HEW funding,


179

Under circumstances of more efficient mass treatment and utillzatlon

of facilities au aseumptlon is made that transplant costs per patient
havedecreasedfrcm$16,000 to$l2,000.  Transplant costs for Individual
non-m supported patients ~lll`remain at about $16,000. HEW expen~ture~~
in support oftraneplantationtreatment nowtotal slpliroldmsteIy$l.Z6,OOO,OOO.
Total expendituresin support oftran&3ntatlon treatment are approdttately

  It is assumed that the mortality mw the transplantees will be
decreased fran k$ to about 3% due to the improved kldneyqatient

mat&lag which ie possible under circumstances of a large program. Among

the 65s who surrtve about one&half are cured; the remdnder return to

chronic dialyslstherapyor ad&nctlve dialysis pending~atlop

The number of patients cured 68 a result of the accelerated tran8plant

progrmn 18 3,575 of which 3,412 ceu~ be attributed to HEW support.

4. Reesarch

  While no specific researchplans wlllbe outlined, itis assumed

that HWresearchexpenditures have increased to atotalof about
$24,700,000 in order to provide support for accelerated laboratory and

clinicalresearchindialyt~le andtransplantation. I?onGEWre~earch

expenditures primarily fromvoluntaryhealth agencies are expected to
be slight in canparWm, i.e., approximately$700,000.

5. TrallrIq

H&l training costs will increase to about $10,000,000 to provide

the necessary training and experience for support of professional

personnel involved In dialysis aud transplant therapy. This trainlqg


will range from formal education in the form of postgraduate fellowships
to on-the-job training.  It is estimated that HIW expenditures will reflect

the total costs in the area of training.

6. Facilities

Facility expenditures by HEW will increase to $5,OOO,OOO and will

be used to aid in the construction of new treatment facilities and

expansion and modification of existing treatment facilities.  Non-HEW

expenditures for facilities are expected to be no more than $800,000.

7. s--Y

  H?ZW expenditures for the entire program are about $210,000,000 with
total costs estimated at $23O,OOO,OOO.  It is estimated that the total

program benefits in terms of mortality avoided will be 7,675 lives

saved of which about 7,000 can be attributed to HEW funding.  A total
of about 16,000 patients can be treated under this program.  Of these,
about 4,900 will die as a combined result of either treatment. Of

those surviving, about 3,600 are cured of kidney disease; because of
transplantation, and about 4,100 are being maintained on chronic

dialysis.

  A summary of the benefits and costs of the program are presented in

Table XV.


Table XV

    END-STAGE UREMIA, HYPOTHETICAL PROGRAM
AT ACCELERATED HEW EXPENDITURE LEVEL, BASED ON THE CURRENT STATE OF THE ART

Transplant

Research

Facilities

Short-Term Benefits

Reduction in Mortality for 1966

HEW Program

7,012   I  7,675     I


E.  End-Stage Uremia, Hypothetical Program for 1975, Accelerated Funding
  Level and Advanced State of the Art

1.  Introduction

This program has five components consisting of:
1) Treatment by dialysis,
2) Treatment by transplantation,

3) Research,
4) Training, and

5) Facilities.

  This program assumes that a number of advances have been made in
the state of the art in dialysis and transplantation (see below). It
is also assumed that progress in research and development in the primary
kidney disease areas has not reduced the annual number of uremic deaths

significantly because of implementation lag time.  The major emphasis
in this program is on transplantation since this procedure requires

only a single treatment, thus about 60$ of all patients are being trans-

planted.  Total program costs acre approximately $162,000,000 of which
about $149,000,000 is being expended by HEW.  A summary of program costs

is presented graphically in Figure 17.  A discussion of the various

program components follows.

2. Dialysis Treatment

It is assumed that a simplified dialysis treatment has been developed
which can be performed by the patient essentially independent of hospital

or clinic facilities. Because of advances in the state of the art, the
debilitating side effects of dialysis therapy have been largely eliminated.
It is estimated that the annual overall mortality among chronic dialysis
patients has been reduced to 5$.  A total of about 12,000 patients are


as ($1,000,000>

1

-









-







-

-

Treatment                        Treatment

(132)

(145)

(1.5) L              +- Research-
    Training (5)

       Facilities
        (10)

HEW

PROGRAM

Training (5.5)

Facilities
(10)

TOTAL

11.5)

Fig. 17+  End-Stage Uieu,ia, Yypothetical Program Costs for Fiscal Year
     1975, At Accelerated HEW Expenditure Level, Based on Expected
      Advanced State of the Art in 1975.

181a


now being treated.  Because of the availability of ample HEW funds
only about 650 patients are being supported by other (VA and private)

funds. The majority of these patients are "Carry-OVerS" from previous


years.

  The cost to HEW and VA for maintaining dialysis patients has

decreased to an absolute minimum of about $3,000 per patient per year

largely due to advances in technology and supplies, including disposable

materials.  Costs for private patients are estimated to be about $5,000

annually.  About $34,000,000 will be expended by HE%? for dialysis

treatment during the first year this program is in effect. Total costs

for dialysis treatment are estimated to be about $37,000,000.

The total mortality avoided (lives prolonged) as a result of this

program is about 11,400 of which some 10,800 can be attributed to HEW

funding.  Please note that these benefits are only for the first year

that the program is in effect.

3.  Transplant Treatment

  Because of advances in the state of the art, the transplant program

encompasses a highly effective organ matching and organ preservation

system.  Immunosuppressive techniques have become highly developed

and successful.  The procedure can now be carried out in most of the

general hospitals in the United States.  Overall annual survival among

transplantees has increased from 65 to 90$ and it is assumed that all

survivors of the transplant procedure are cured.  A total of about
17,750 kidney transplant procedures are being performed annually of which
HEW supports about 16,350.


283

The coat of total patient management by tr8n!3pl8n$xktlon withln

Federalprogremsh8s beenreducedto &out$6,OOObeqause of easier

matching of organs, 8 decre8se in graft-I3?jCCtiOE3 XWWtiOXW, rpld 8

decreased need for sdjunctive dialysis.  Ron-Federal transplantation

costs are about $8,000 per patient.

The number of patients cured due to the total transplant prograu

efforts is 8pproxLm8tely 16,000 of which &out 15,ooO can be attributed

to mu funding.

4. Resessch

Because of previous research achievements,HEWreee8rchexpendltures
have decreased considerably to an annual. level of $1,500,000. It is
8ntfclpated that there will be no support for resecrrch by other sources.

5. waning
HEW training expenditures are estimated to be $5,000,009 to provide
for the necessary professional 8nd 8lUed personnel required In the

treatment progrsm.  It is anticipated that because of the availability

of HEW fUnda, there will be no expenditures from other sources for

training.

6. Facilities

Facilities expenditures are estimated to be $~O,OOO,OOO and are

used In establishing or maintaining the canplex of treatment facilities

requlredforthls program.  An 8dditlon8l$8OO,OOO%s estimatedtobe

spent by other sources=

7.summary

HEW expenditures for this prograDD are estlm8ted 8t 8bout$148,000,000.
Total program costs are estimated to be about $102,000,000. Total mortality


184

avoided because of this program till be about 27,000 lives of which
about 26,000 will be attributed to HEN.

The above program sustains about 11,400 dialysis patients and about
16,000 transplantees during the first year the program goes into effect.
The majority of the dialysis patients (about pC$> would be carry-over

patients from previous years.  These patients include transplant rejects

as well as uremic patients unsuitable for transplantation.

A summary of the benefits and costs of this program is presented in

Table XVI.


END-STAGE UREMIA, HYPOTHETICAL PROGRAM FOR FISCAL YEAR 1975

AT ACCELERATED HEW EXPENDITURE LEVEL, BASED ON EXPECTED ADVANCED STATE OF THE ART IN 1975

Short-Term Benefits

   Programs


Dialysis
Transplant

Research

Training

Facilities


      Totals

    Expenditures
($ Em     Total
      (9 1,000)


34,125     36,775
98,100.    108,100
  1,500      1,500
  5,000      5,000
10,000     10,800

148,725.    162,175

Reduction in Mortality for 1966

HEW Program    Total Program
(No. of Lives) (No. of Lives)


  10,806        11,424
  14,715        15,975

              I



  25,521       27,399


REFERENCES AND FOOTNOTES

In 1964 there were 10,297 deaths recorded under ICD codes 600, 605, 607,
and 640 (United States Department of Health, Education, and Welfare,
Vital Statistics of the United States, Vol. II - Mortality Part A,
Washington, D. C.:  U. S. Government Printing Office, 1966, p. l-68).
The 1966 estimates were derived by multiplying the 1964 deaths by the
ratio of the total United States population in 1966 versus 1964
(1.0246).  Bureau of the Census, "Estimates of the Population of the
United States by Age, Color, and Sex; July 1, 1960 to 1965," Population
Estimates, Series P-25, No. 321, November 30, 1965, p. 11 and Bureau of
the Census, "Estimates of the Population of the United States by Age,
Color, and Sex; July 1, 1966, "Population Estimates, Series P-25, No. 352,
Nciv. 18, 1966, p. 1.

It is estimated from the Division of Health Interview Statistics,
National Center for Health Statistics, U. S. Department of Health,
Education, and Welfare, report (unpublished), that in fiscal year
1965 the civilian non-institutional population had an estimated preva-
lence of 1,933,OOO cases of infectious diseases of the kidney with an
associated 37,535,OOO days of restricted activity (an average of 19
days per case), 17,012,OOO days of bed disability, and 4,121,OOO work-
loss days.

In order to take into account population changes for 1965 to 1966, the
above morbidity statistics were corrected by a factor of 1.0156.  ThiS
reflects the increase in population--Bureau of the Census, "EstFmates
of the Population of the United States by Age, Color, and Sex; July 1,
1966," Population Estimates, Series P-25, No. 352 (November 18, 1966),
p. 1 and Bureau of the Census, "Estimates of the Population of the
United States by Age, Color, and Sex; July 1, 1960 to 1965," Population
Estimates, Series P-25, No. 324, (November 11, 1965), p. 11.

The corrected statistics yielded an estimated prevalence of 1,963,OOO
with an associated 38,197,OOO days of restricted activity, 17,277,OOO
days of bed disability, and 4,185,OOO work-loss days.

Edward H. Kass, "Asymptomatic Infections of the Urinary Tract,"
Transactions of the Association of American Physicians, Vol. 69, 1956,
p. 56-64.

Alan L. Kaitz, and Elizabeth J. Williams,
Infections in Hospitalized Patients,"   "Bacteriuria and Urinary-Tract

Vol. 262, No.              The New England Journal of Medicine,
      9, (March 3, 1960), pp. 425-430.

Edward H. Kass, "Bacteriuria and Pyelonephritis of Pregnancy,"
of Internal Medicine, Vol. 105 (1960), pp. 257-264.          Archives

Ruth Osterby Hansen, "Bacteriuria in Diabetic and Non-Diabetic Out-Patients$"
Acta Medica Scandinevica, Vol. 176, No. 6 (1964), pp. 721-730.


186

Admissions to non-federal long-term general hospitals, non-federal short-
term general hospitals and federal general hospitals were used to derive
the hospitalized population.  In 1965 these totalled.28,184,957.
Hospitals, Vol.. 40, Part 2 (August 1, 1966), pm 442.

In order to take into account population changes and to provide estinrstes
for 1966, we corrected the 1965 hospital admissions by a factor of 1,56X
(see Footnote 2 above) for a total of 28,625,OOO.

The resident population in nursing homes was derived from National Center
for Health Statistics, "Characteristics of Residents in Institutions for
the Aged and Chronically Ill in United States, April-June'1963,' Vital
and Health Statistics, Series 12, No. 2, p. 19, and amounted to S-2
residents in 1963.

The Nursing Home population was corrected for increases in the population
65 years and over from 1963 to 1966 by a factor of 3.37% (the sources
for this factor are the ssme as the ones described above.for the hospital
admissions).  The new estimate is 522,000 residents in nursing homes.

The total relevant population for 1966 is estimated at 29,147,OOO.

The number of pregnant females for fiscal year 1965 was taken from
National Center of Health Statistics, "Current Estimates from the National
Health Interview Survey, United States, July 1964 - June 1965,' Vital and
Health Statistics, Series 10, No. 25, November 1965, p. 5. The published
number of 4,472,OOO was corrected for the increase in population for
females between 20 and 45 years of age. The correction factor was .57X
(Bureau of the Census, 'Estimates of the Population of the United States
by Age, Color, and Sex; July 1, 1966,' Population Estimates, Series P-25
No. 352 (November 18, 1966), p. 15, Bureau of the Census, "Estimates of
the Population of the United States by Age, Color, and Sex; July 1, 1960-
1965," Population Estimates, Series P-25, No. 324 (November 11, 1965),
p. 11.  The new estimate is 4,497,OOO.

The estimated number of non-hospitalized diabetics was obtained from
unpublished data from the National Center of Health Statistics. The
unpublished estimates showed a prevalence of 2,385,OOO. Taking into
the account the increase in population from 1965 to 1966 of 1.56% (see
Footnote 2) we arrived at a new estimate of 2,422,OOO.

See Footnote 4.

36,066,OOO individuals divided by 6,462,520 cases of significant
bacteriuria.

Based on informed medical judgment.

The estimate of 5% false positives was based on informed medical judgment.

A "best estimate."


187

13/
-

141
-

151
-

161
-

171
-


18/
-

191
-

19A/

201
-

a/

w
-

23/
-

241
-

25/
-

26/
-

271
-

28/
-

w
-

30/
-

31/
-

32/
-

36,066,OOO indivfduals in the. karget'populaticm tfam?".$0.25.

Based on patient charges from Duke University Hospital, Durham, N-C.

A "best estimate."

A "best estimate."

It was felt that 65% of the deaths could be attributed to the relevant
population, or 6,800 from a base of 10,550 (see Footnote 1).

Based on informed medical judgment.
It'is estimated that of the 19 average morbid days per individual (see
Footnote 2), only 20% should be attributed to infections of the kidney
because all of the high-risk groups have other primary diagnoses. The
prevalence was multiplied by 19 days and then corrected by the 20% factor.

The specific relationship between infections of the urinary tract and
end-stage kidney disease due to chronic pyelonephritis is still subject
to conjecture.  The estimates made here are based on the assumption of
a cause and effect relationship between bacteriuria and chronic pyelonephritis.

Based on informed medical judgment.

Based on informed medical judgment.

All the estimates in this paragraph were based on informed medical judgment.

A "best estimate."

A "best estimate."

A "best estimate W
                  .

Based on informed medical judgment.

Bureau of the Census, "Estimates of the Population of the United States
by Age, Color, and Sex, July 1, 1966," Population Estimates, Series P-25
No. 352 (November 18, 1966), p. 17.

A "best estimate."

C. Kunin, T. Southall, and A. J. Paquin,
Infections.                 "Epidemiology of Urinary-Tract

of Medicine, A Pilot Study of 3,057 School Children," New England Journal
      Vol. 203 (1960), p. 817.

A "best estimate."

The Prevalence base used is the one derived from the 1% or 25,200 detected
cases with significant bacteriuria among females 6. to g years of age.

See Footnote 19.


36/
-

371

Jy

391

40/
-




31

Based on informed medical judgment.

Based on informed medical judgment.

The estimated total number of detected cases of significant bacteriuria
in the 6 to 9 years of age female group.

Based on informed medical judgment.

Based on informed medical judgment.

See Footnote 27.

S. Switzer, "Bacteriuria in a Healthy Population and Its Relation to
Hypertension and Pyelonephritis," New England Journal of Medicine, Vol.
264 (1961), p. 7.

Since 12,319,500 are expected to be screened each year and 1% or 123,195
are estimated to have significant bacteriuria, then if 85% (104,716) will
be detected, 109,952 (104,716 x 105%) will show a positive screening test
result.

It was felt that about 60% of the 41,065 females 21 years of age and under
can be reached.  Of these 24,639,OOO females, the screening program would
reach one-half each year or 12,319,500.  One percent of these or 123,195
would have bacteriuria.

From a prevalence baae of 123,195, 2,340,710 morbid days were calculated by
using an average of 19 morbid days per individual (unpublished data from
National Center of Health Statistics).

Based on informed medical judgment.

Based on informed medical judgment.

Based on informed medical judgment.

Based on informed medical judgment.

Bureau of the Census, "Estimates of the Population of the United States
by Age, Color, and Sex; July 1, 1960 to 1965," Population Estimates,
Series P-25, No. 352 (November 18, 1966), p* 1, and Bureau of the Census,
"Projections of the Population of the United States by Age, Sex and
Color to 1990, with Extensions of Total Population to 2015," Population
Estimates, Series P-25, No. 359 (February 20, 1967), p. 14.

See Footnote 4.

See Footnote 4.

See Footnote 4.

See Footnote 39.


521

Jg

54/
-

551
-

561
-

x/

58/

$21

63/
-

641
-

65/
-

661
-

67/
-

These include all high-risk groups adjusted for population changes.

A "best estimate."

Based on informed medical judgment.

Based on informed medical judgment.

Based on informed medical judgment.

Based on informed medical judgment.

Based on informed medical judgment.

Based on informed medical judgment.

Based on informed medical judgment.

In 1964 there were 12,414 deaths recorded under ICD codes 590-594
(U. S. Department of Health, Education, and Welfare, Vital Statistics
of the United States, Vol. II - Mortality Part A, Washington, D. C.:
U. S. Government Printing Office, 1966, pp. l-68).  The 1966 estimates
were derived by multiplying the 1964 deaths by the ratio  of the total
United States population in 1966 versus 1964 (1.0246),
(See Footnote 1.)

It is estimated based on data from the Division of Health Interview Statistics,
National Center for Health Statisbics, U. S. Department of Health,
Education, and Welfare report (unpublished), that in fiscal year 1965
the civilian non-institutional population had an estimated prevalence
of 104,000 cases of hypersensitivity diseases of the kidney with an
associated 4,011,OOO days of restricted activity (an average of 40
days per case), 1,806,OOO days of bed disability, and 765,000 work-loss
days.  Taking into account the population increase from 1965 to
1966 (correction factor of 1.0156; see Footnote 2), the prevalence
is estimated at 106,000 with an associated 4,074,OOO days of
restricted activity and 1,834,OOO days bed disability as well as
777,000 work-loss days.

See Footnote 61.

A "best estimate."

Based on informed medical judgment.

Based on informed medical judgment.

Estimated from unpublished data from the National Center for Health
Statistics.

68/ Based on informed medical judgment.
-


69/ Based on informed medical judgment.
-

70/
-  Based on informed medical judgment.
71/ Based on informed medical judgment.
-

721
-

a!

741
-

75/
-

76/
-

771
-

B/

79/
-

80/
-

f3U
-

W
-

831
-

841
-

Based on informed medical judgment.

John I. Levit, "The Prognostic Significance of Proteinuria in Young
College Students."  Annals of Internal Medicine, Vol. 66, No. 4,
(April 1967), pp. 685-698, and Maurice B. Strauss and Louis G. Welt,
ed., Diseases of the Kidney, Boston: Little, Brown and Company, 1963,
pp. 80-88.

Ibid.

Ibid.

Ibid.

The estimate of 1966 deaths of 12,719 (see Footnote 61), was corrected
by the change in population factor of 1.14% (see Footnote 46).

Based on informed medical judgment.

The 20,000 cases with hypersensitivity diseases were multiplied by 40
morbid days (unpublished data from the National Center for Health
Statistics) to arrive at 800,000 morbid days.

Based on informed medical judgment.

Based on informed medical judgment.

See Footnote 47.

Maurice B. Strauss and Louis G. Welt, ed., Diseases of the Kidney,
Boston:  Little Brown, and Company, 1963, p. 505.

In 1964 there were 69,634 deaths recorded under ICD codes 440-447
(U. S. Department of Health, Education, and Welfare, Vital Statistics
of the United States, Vol. II - Mortality Part A, Washington, D. C.:
U. S. Government Printing Office (1966), pp. l-68). The 1966 estimates
were derived by multiplying the 1964 deaths by the ratio  of the total
United States population in 1966 versus 1964 (1.0246). (See
Footnote 1.)

851 Based on informed medical judgment.


861
-

871
-

881
-

921
-

93/
-

941
-


B/

961

1t is estimated based on data from the Division Of Health Interview Statistics,
National Center for Health Statistics, U. S. Department of Health, Education,
and Welfare report (unpublished), that in fiscal year 1965 the civilian non-
institutional population had an estimated prevalence of 9,187,OOO cases
of hypertension with an associated 147,126,OOO days of restricted activity
(an average of 16 days per case), 54,638,OOO days of bed disability (an
average of 6 days per case), and 7,948,OOO work-loss days (an average of
1 day per case).  Taking into account the population increase from 1965
to 1966 of 1.0156 (see Footnote 21, the prevalence is estimated at
9,330,OOO in 1966.  To this is added an estimated 2,100,OOO cases which
are undiagnosed for a total of 11,430,OOO hypertensives in 1966.
Applying the same correction factors to the different classifications of
morbid days and taking into account the undiagnosed cases, estimates of
181,280,OOO days of restricted activity, 68,580,OOO days of bed disability
and 11,330,OOO work-loss days are derived.

H. Brainerd, et al., Current Diagnosis and Treatment, Los Altos, Calif.:
Lange Medical Publication, 1966, p. 201.

Paul B. Beeson, and Walsh McDermot, Textbook of Medicine, Philadelphia:
W. B. Saunders Co., 1963, p. 712.

It is estimated that 20% of the costs of curing those currently curable
hypertensives who have renal complications (50% of these hypertensives)
is attributable to renal causes, or 10% of the total cost.

A "best estimate "
                  .

Twenty percent of the 85% (7,930,OOO) with currently non-curable hyper-
tension.

It is estimated that 20% of the costs of curing those currently non-
curable hypertensives who have renal complications (27% of these hyper-
tensives) is attributable to renal causes, or 6% of the total
cost.

See Chapter 6, Section B.a.

Based on informed medical judgment.

Since only .8% of the hypertensives are being considered it is assumed
that they would account for .8% of the hypertensive deaths in 1966 or 570.

Based on informed medical judgment.

Estimated from unpublished data from the Division of Health Interview
Statistics, National Center for Health Statistics, U. S. Department of
Health, Education, and Welfare.

971
-  Based on informed medical judgment.


981  Since approximately 70% of the hypertensive8 are being considered in
  this group, it Is assrrmed that these would account for 70% of the estl-
  mated d.eaths in 1966, or 49,940.     
z/ Morbid days were obtained by multiplying the affected prevalence of
  1,586,OOO (see Footnote 86) by 16 days, the average number of days
  of restricted activity for.each case (see Footnote 84).

ml It was assumed that the average remaining life span of each hyperteusive
   was 20 years, Henry.Brainerd, et al., a. cit., p. 207, aud the expected
                                        -.-
   cumulative nmber of cases of end-stage uremia, 98,000, see Chapter 6
   Section B.2.c,(2), was divided by 20.                    
ml Again, assuming that the average life span of hypertenslves is 20 years,
   the expected nmber of cumulative cases of end-stage uremia, 277,550,
   see Chapter 6, Section B.2.c.(2), was divided,by 20.
102' Based on informed medical judgment.

1031 Based on informed medical judgment.

1041 These estimates are derived from the present level of effort in the
  renal hypertension program of NIL                    
`&%I These estlniates are derived fran the present level of effort in the
   renal hyperteusion program of NIE.

k@/ These estlmates are derived from the present level of effort in the
   renal hyperteusiou program of NIH.

1071 `IQo-thirds of the population has been estimated to have se4 a physician
   within a year prior to interview.  (National Center for Health Statistics,
   "Age Patterns in Medical Care, Illness, and Disability, United States -
   July 1963 - June 1965," Vital and Health Statistics, Series 10, No. 32,
   June 1966, p. 12.) The estimated population of the United States in
   1966, 17 years of age and over is 130,640,750.  (Bureau of the Census,
   "Estimates of the Population of the United States, by Age, Color, and
    sex:  July 1, 1966," Population Estimates, Series P-25, No. 352, Nov. 18,
   1966, p* 14.) Applying a factor of one-third to the population, we      .

   arrive at a rounded estimate of 43,500,OOO.

g Based on informed medical judgment.
109/ A "beet est%mate" taking into account Intermediate progrsm level
   budgetary constraints.

1101 Since approximately 0,2X of the total hypertensive8 Is affected each
   year by this program sub-component, 0.2% of the 71,347 estimated deaths
   or 140 deaths are expected to occur yearly without the new program effort.


593

&!,&/ prevalent-e was derived by taking 15% (see Footnote 85) of the expected
  175,000 newly detected hypertensives, or 26,250.

112/  The prevalence of 26,250 was multiplied by the average 16 days of
  restricted activity per case of hypertension (see Footnote 86).

1131  Since approximately 1.5% of the total hypertenslves is affected by this
   program sub-component, 1.5% of the 71,347 estimated deaths, or 1,070
   deaths are expected to occur yearly without the new program effort.

1141 The prevalence of 148,750 [85% ( see Footnote 85) of the expected 175,000
  newly detected hypertensives] was multiplied by the average 16 days of
   restricted activity per case of hypertension (see Footnote 86).

1151
-  Assuming that the average life span of hypertensives is 20 years, the
   expected number of cumulative cases of end-stage uremia, 11,025,
   (see Footnote 117), was divided by 20.

1161 Again, assuming that the average life-span of hypertensive8 is 20 years
   the expected number of cumulative cases of end-stage uremia, 31,240,
   was divided by 20.

117/ Seven percent, of the 157,500 (15% of the 1,050,OOO newly detected
   hypertensives), or 11,025 patients with currently curable hypertension are
   estimated to progress eventually to end-stage uremia without this program
    sub-component.

1181

3.5% of the 892,500 (85% of the 1,050,OOO newly detected
hypertensives), or 31,240 patients with currently non-curable hypertension
are estimated to progress eventually to end-stage uremia without this program
sub-component.

G/ Based on informed medical judgment.

120/

   Since approximately 0.4% of all hypertensives are affected each
   year by this program sub-component, 0.4% of the 71,347 estimated deaths
   or 290 deaths are expected to occur yearly without this new program effort.
1211  The prevalence was derived by taking 15% (see Footnote 87) of the
   expected 350,000 newly detected hypertensives.

1221 The prevalence of 52,500 was multiplied by the average 16 days of
    restricted activity (see Footnote 86).

12' Since approximately 3% of all hypertensives are affected each year
   by this program sub-component, 3% of the 71,347 estimated deaths, or
  2,140 deaths are expected to occur yearly without this new program effort.
=' The Prevalence of 297,500 [85X (see Footnote 87) of the expected 350,000
  newly detected hypertensives] was multiplied by the average 16 days of
   restricted activity per case of hypertension (see Footnote 86).


`34

125' The estimated population 17 .years of age and over in '1975 Is 150,554,OOO
   (Bureau of the Census, ."Projections of the Population of the United
   States by Age; Sex , and Color to 1990, with Extensions of Total Popula-
   tion to 2015," Population Estimates, Series P-25, No. 359, February 20,
   1967, p. 14).  The estimated population of 17 and over in 1966 is
   129,746,OOO (Bureau of the.Census, "Estimates of the Population of the
   United States, by Age, Color, and Sex: July 1, 1966," Population
   Estimates, Series P-25, No. 352, November 18, 1966, p* 14). The ratio
   of the 1975 to 1966 population'17 years of age and over is 1.16.
                                                                           

- A "best estimate."
126/

127/
-  It was assumed that approximately 30% of all hypertensives would have
   some associated reual problem aud that 20% of their total treatment
   costs would be attributed to the treatment of the reual complication;
   therefore, 6% of $10,997,000, or $660,000, was attributed to renal
   complications.

128' The vital statistics bases are derived iu the same,way as those in the
   1966 accelerated progrsm with the addition of'l6X for anti,cipated
   increases in the population 17 years of age and over in 1975. Expected
   benefits take into account probable advances in the state of the art
   (see Chapter 6, Section E.6.).

1291 See Footnote 127.

m/ The benefits are the sum for all high-risk groups described and take
   into account 1) the 1975 population 17 years of age and'over, and 2)
   the change in benefit rates due to advances in the control of the diseases
    discussed.

1311 The number of uremic deaths is based on conservative estimates from
   unpublfshed data gathered during a study conducted by the Besearch
   Triangle Institute, Researdh Triangle Park, North Carolina, entitled:
   Estimation of a Chronic Hemodlalysis Population, March 1967.

132'  Ibid.

1331 The estimate of ideal transplant candidates was based on informed
   medical judgment .

m/ Unpublished data from the ongoing study, Soclo-Economic Status of
   Dialysis Patients, Berkeley, California, University of California
    Medical Center.

='  Ibid.

1361 IJ. S. Veterans Administration, unpublished data on Inpatient Mortality,
   Morbidity, and Treatment Costs, April 1967.


1371
- B. H. Scribner, "Hemodialysis in the Treatment of Chronic Uremia,"
    Abstracts, III International Congress of Nephrology, Vol. I:  General
   Sessions--Symposia, Washington, D. C.: 1966, pp. 43-44.

138/ The total and HEW end-stage uremia programs costs for dialysis treatment
   were calculated on the basis of average annual costs of dialysis per
    patient.

139/  The dialysis-mortality estimate was based on informed medical judgment
   and unpublished data from the Kidney Disease Control Program, National
    Center for Chronic Disease Control.

140/  Public Health Service, U. S. Department of Health, Education, and
    Welfare, Kidney Diseases:  1968 Issue Paper and Appendices, Washington,
     D. C.:  U. S. Government Printing Office, July 1966.
1411
-  Transplantation costs are based on informed medical judgment.

1421 The total and HEW end-stage uremia program costs for transplantation
   treatment are based on the average annual costs of transplantation per
    patient.

1431

Based on recent unpublished report "Fifth Report of the Human Kidney
Transplant Registry," Department of Surgery, Harvard Medical School,
the Peter Bent Bingham Hospital, the Massachusetts General Hospital,
and the Harvard Computing Center.

144/
-  The transplant cure rate is based on informed medical judgment.
x/  Kidney Disease Issue Paper, *. cit.

1461  Training expenditures were based on unpublished data and expert opinion.
1471  Facility expenditures were based on unpublished data and expert opinion.


Chapter 6

The Cost of Treating All Patients with Chronic Kidney Failure

                             :

I.  INTRODUCTION

Whenever consideration is given to the problem of kidney diseases,

including end-stage kidney disease or:progressive, ultimately fatal

chronic renal failure, the question arises of the overall cost of treat-

    patients threatened by a uremic death; either with the aid of

lifelong msintenance on dialysis or through 8n attempt at kidney trans-

plantation whenever donor kidneys may be aV8ilUble. Although the original

                                                                      . . .

mission of the Kidney Disease Analysis Group did not include the preparation

of an answer to this question It wus felt that an analysis of this cost

would be a natural corollary to the preceding analyses of costs and benefits

of optimal programs aimed 8t the major primary kidney diseases and at end-

stage kidney disease.  In any consideration of possible programs for the

amelioration of the kidney disease problem, the overall expense of treating

all patients threatened with a uremic death regardless of the possible costs,

for humanitarian reasons, represents one extreme in a broad spectrum of

possible programs.  It should therefore be ascertained to serve 8s a m8xlmal

bench mark for any intensive attempt at program analysis or planning.

11.  APPKOACH TO THKTOTALTKKATMKNT OF END-STAGE
             KIDNEY DISEASE

A. General Assumptions

In this particular hypothetical situation it is assumed that 8 population

of 50,000 individuals exists who are threatened by death from end-stage


kidney disease during the first year of the projected program.   It is

known that approximately three-fourths of this population is above the

age of 60.  The available modes of treatment are primarily lifelong dialysis

and transplantation.

  For the purposes of this analysis an assumption is made that the

change in population size during the following few years can be disregarded.

Likewise this analysis assumes that any existing programs aimed at the

amelioration of primary kidney diseases do not affect to a significant

extent the figure of the vulnerable end-stage kidney disease population,

at this point.  This analysis as,sumes that there are no restraints on the

availability of well-trained, competent physicians and other necessary

personnel to administer the available treatments and on facilities needed

for dialysis and transplantation.  In reality such a "total push" program

could not be undertaken all at once because of the above restraints,

particularly because of the lack of sufficient qualified and willing physi-

cians.

B.  Treatment Modalities


   1.   Conservative Treatment


     Conservative treatment, primarily by diet and symptomatic therapy

will be reserved for a certain proportion of the vulnerable population,

namely those extremely old and beset with other intercurrent complicating
diseases which would make them unacceptable for major surgery and

extremely poor risks for prolonged dialysis.  (Also included in this

list would be those individuals who, for a variety of other reasons are

not suitable for chronic dialysis, or who refuse either treatment.> It

is assumed that about 10,000 individuals out of the total vulnerable

population of 50,000 belong in this category. A more conservative view
maY Place the former figure at 15,000 to 20,000.


398

2.  Transplantation

projections for this treatment are based on the present state of

the art.  However, to make such a large-scale treatment program by

transplantation possible at all it is assumed that efficient methods
for collection of cadaver kidneys are in force and that existing legal
barriers to tissue taking have been overcome. In addition, it is
assumed that donation of kidneys upon death has become a popularly

accepted procedure.  In the subsequent calculation it is taken for

granted that generally there will be no transplantation in patients

over the age of 60 because of the highly increased operative risk and

the many concurrent secondary disorders or complications found in this

age group.

Of the 50,000 vulnerable patients, 10,000 will be treated by

conservative means only (please see above).  Of the remaining 40,000

candidates, 2,000 would meet ideal criteria for transplantation.
Such criteria include not only optimal state of the patient's health

(aside from his renal defect) but also the changes of optimal tissue

matching with available kidneys.  An additional 9,000 individuals would

meet satisfactory criteria for transplantation.

  In the group of ideal candidates it is expected that about 80

percent would be cured, and that approximately an additional 10 percent
would survive but their transplanted kidneys would fail and they would

require chronic dialysis for survival; an ,additional 10 percent would
probably die directly due to the surgery or due to the sequellae of
their operation or because of eventual immunosuppression therapy which
makes them susceptible to overwhelming infections.  In the group of

Satisfactory candidates the respective figures would be approximately


30 percent, 30 percent, and 40 percent.
On the average, it can be assumed that among the 11,000 patients

in whom transplantation would be attempted, about 30 to 35 percent

will be cured, an additional 30 to 35 percent would survive but

would have to be returned to dialysis because of eventual failure

of the transplanted kidney, and about 35 percent would die.

  A small number of eventual secondary kidney failures may be

expected among patients who were originally thought to be cured by
                       

transplantation.  Most of these cases would probably represent

development of glomerulonephritis in the transplanted kidney in

patients in whom this disease was the original cause of renal failure.

me assumption is made in the calculations to follow that these patients

would be counted in the general reservoir of 50,000 vulnerable individuals

who.present themselves each year in need of treatment because of end-stage

chronic kidney failure.

  Based on the considerations and percentages mentioned above, of the

11,000 patients treated by transplantation each year, about 3,575 would

be cured, an additional approximate 3,575 patients will have to be

returned, eventually, to dialysis treatment, and approximately 3,850

will die during that year or soon thereafter.

3.  Chronic Dialysis

  Projections for this treatment are based on the current state

of the art.

Of the 50,000 vulnerable patients, 10,000 will be treated by

conservative means only, and of the remaining 40,000 candidates, 11,000
will be subject to transplantation (please see above).  Thus, in any


one year there remain 29,000 patients who would be placed on chronic

dialysis.  In reality, conservative medical opinion  may hold that many
of these patients are not promising candidates for chronic dialysis. In
addition there will be a group of about 3,575 patients each year who would

be placed on  chro Is% 1~ dialysis treatment because of eventual failure of

their transplanted kidney (see above).

  Among the large group of individuals who are candidates for

chronic dialysis treatment there is a small group of highly suitable

patients for dialysis.  Based on current experience in the United

States there is a yearly survival rate of 90 percent among such

individuals on chronic dialysis.  The majority of vulnerable individuals,

however, cannot be considered good risks for chronic dialysis treatment

under present conditions.  At present, such patients would not be
acceptable to the small number of existing dialysis programs in the

United States.  On the other hand, there has been considerable experi-

ence with such patients in many European centers who are accepting
patients for chronic dialysis not on the basis of strict medical,

psychological and socioeconomic admission criteria, but on the basis

of patient need.  The yearly survival rate for such patients is only
about 50 percent during the first year and varies from 50 to 90 percent

in subsequent years.

There is a great overlap in the groups which are considered ideal
for transplantation and ideal for chronic dialysis and since trans-
Plantation will be attempted in those ideal or near-ideal for this

purpose, the majority'of patients in the chronic dialysis program skill at
best be satisfactory or high-risk patients. Based on the above considera-

tions and percentages, the overall assumption was made that the survival

rate in chronic dialysis for the first year of treatment will be 50
Percent and that the survival rate in subsequent years among the remaining



patients will be 90 percent.

  Thus, on the average it can be assumed that of the 29,000 new

patients treated by chronic dialysis each year, about 14,500 will

survive and 14,500 will not survive the first year of treatment.

The 14,500 survivors (now depleted of the poorest risks) will sub-

sequently have a 90 percent survival rate in the ensuing years.

In addition, of the approximate 3,575 brought into the dialysis
program each year after an initial unsudcessful attempt at trans-

plantation, approximately 3,218 will survive the first year because

they were derived from a strongly overlapping group of highly suitable

patients for either treatment.

III.  CALCULATION OF COSTS

A.  Yearly Costs

  It is obvious that the mere calculation of the cost of the first year

of such a "total push" programwould leave a misleading impression as to

the true long-term expense involved if such an approach is chosen.   Because



? of the significant rate of survival from year to year among the patients

treated by chronic dialysis the cost of extending treatment to all those

needing it in subsequent years will increase considerably with the passage of

time.  It was therefore decided to calculate the actual cost of the treatment

of & individuals requiring it (the new group of vulnerable uremic patients

presenting itself each year and the patients on lifelong dialysis who are

survivors from Previous years) for as many years as needed after the start Of

the program until a year was reached which could be considered characteristic

of a "steady state."  At this particular point in time the number of new

Patients included each year in this program would equal the number of patients


202

dying in the same year, and in this situation a constant or near-constant

yearly cost of the program would be reached.

Calculations to find a year in which a steady state would be reached

showed that under the conditions of this program its yearly cost would
increase greatly each year during the first 15 years, that the subsequent

yearly increases in cost would be of a somewhat lesser magnitude but still

highly significant, and that an asymptotic curve approach would show that

the steady state would not yet be reached by the twenty-fifth year.  Obviously

one can expect research advances to occur well within the first 10 or 15 years

(provided that current Federal research support will not be diminished because

of the institution of a "total push" treatment program) and that these

advances would modify greatly the respective efficacies of transplantation

and hemodialysis and their costs.  It was therefore decided that it would be

unrealistic to report the cost of the hypothetical total push treatment

program for end-stage kidney disease in terms of the eventual yearly cost of

the steady state after 25 years.  Rather, it was felt that it would be

sufficiently indicative of the true costs to be expected to report the cost
of the first year of such a program (the lowest yearly cost), the cost of
the fifth year (a realistically foreseeable sum which is not likely to be
influenced significantly by changes in the state of the art), and the cost
of the fifteenth year (which is considerably higher than the cost of the fifth
year and begins to approach the markedly higher eventual cost of the steady

state year).

Based on the conditions in II A and II B, above, the yearly costs for this

program were calculated for each of the first 15 years. As expected, the total
cost of this treatment program rose considerably and progressively with each
                        .
Year because of the significant carry-over, from the preceding years, of

surviving patients on chronic dialysis.


203

B.  Present and Future Per Capita Costs

  TO obtain a realistic range of cost the CalCUlatiOnS were done on the

basis of two cost assumptions for each treatment modality:

  1) A "present cost" figure of $16,000 per patient for transplantation,

and a "present cost" figure of $15,000 per year per patient for chronic dialysis,
The latter figure reflects as accurately as possible the present cost of chronic
dialysis in a specialized dialysis center setting.  (Dialysis at home was

not yet considered well enough developed to be proposed for this large

population.  Moreover, it was recognized that the majority of patients to

be treated by dialysis did not have the proper home setting, a vigorous and

capable spouse, or other family conditions which are a prerequisite for

successful home dialysis).

  In the case of transplantation, the cost of $16,000 includes all medical

and surgical expenses for the year in which the transplantation takes place,

such as the necessary preliminary dialysis regimen and tissue matching, the

surgery and all postsurgical treatments--dialysis, immunosuppression, and

others--averaged out per patient (since some patients would require more

and some less of these after-treatments).

2) An estimated "future cost" figure for each treatment modality which

should reflect the decrease in cost of these treatments due to the mass

operation effect, such as cost decrements due to greater efficiency of a

large scale, well organized operation in dialysis, and savings due to more

efficient large scale organization of the necessary preoperative, operative
and postoperative activities and treatments in the case of transplantation,
including greater efficiency in matching available kidneys to a large t'issue-

typed panel of recipients.  The "future cost" figure for transplantation
was thus set at $12,000 per patient and, in the case of dialysis, at $10,000

per patient per year.


204

As has been mentioned before, this hypothetical program could not be

started in the intended scale since neither the necessary facilities nor

a sufficient number of specially.trained (and willing) physicians, surgeons,

and paramedical personnel is available.  The present analysis is carried

out, nevertheless, in order to delineate the costs one must expect for such

a total push endeavor.

The "present cost" figures are considered here to hold true for the first

year of this hypothetical program, and may continue to influence costs in

the early years until the gradual, improved organization and integration of

the evolving mass effort permit the eventual cost reductions foreseen. The

considerably lower "future cost" figures would become representative

progressively during the subsequent years.  To allow for all possibilities,

the cost of the various years is reported in terms of a range between the

higher "present cost" figure and the lower "future cost" figure.

  It was decided not to charge the cost of conservative treatment to

this total push program on the basis that the nature of the expenses of

conservative treatment are not much different from those of other semi-

terminal and terminal disease conditions, and that such costs would therefore

not be borne by the Federal Government.

IV.  RESULTS

The following results were obtained on the basis of the previously

explained assumptions and calculations:

A.   First Year

  Based on "present cost" figures, the cost of treating 40,000 patients

out of the total vulnerable population of 50,000 during the first year of

this hypothetical program, by means of chronic dialysis or kidney transplantation,

would be $611,000,000.


   Note:  If an attempt is made to treat all 50,000 vulnerable patients, the
cost of this program during the first year will be $761,000,000.
If the calculation for the first year is based on the less likely

"future cost" rate, the respective figures would be $422,000,000 and

$522,000,000.


B.  Fifth Year

  The cost of this program in the fifth year of its existence will range'

between $1,043,600,000 (based on the low, "future cost" figure) and $1,543,415,000

(based on the higher, "present cost" figure).  In this year, 102,161 patients

will be treated under the program by transplantation or chronic dialysis.


C.  Fifteenth Year
The cost of this program in the 15th year of its existence will range

between $1,816,000,000 (based on the low "future cost" figure) and $2,702,000,000

(based on the higher "present cost" figure).  In this year, 179,401 patients

will be treated under this program, by transplantation or chronic dialysis.

  In view of the fact that it is anticipated that research advances '

evolving during and after the first fifteen years of the program would
introduce considerable improvements into both treatment modalities and would

influence true costs significantly, projected expenses for the twentieth and

twenty-fifth year of the program are not given.  It should be noted, however,
that the population which would require treatment during each year of fhis

program will continue to grow and thus the yearly costs will increase, until
a point beyond the twenty-fifth year at which a steady state will be reached.


206

V.  DISCUSSION

  The cost figures cited in the foregoing section are likely to be

discouraging to any but the most determined advocates of a total push


program.  In reality, however, other factors which are more compelling

than dollars are even more important in consideration of attempts at

large scale treatment of end-stage kidney failure. Among these are 1)

the nature of the population of 50,000 who present themselves each year

with end-stage kidney failure, 2) the availability of trained and qualified

physicians for the dialysis component of such a program, and of surgeons

and physicians for its transplantation component, 3) the availability of

the necessary competent and well-trained paramedical staff, and 4) the

availability of necessary facilities for large scale chronic dialysis,

be it in a hospital setting or in specialized dialysis centers associated

with existing hospitals.

  Assuming that one well-trained and willing physician is necessary for

every 10 to 20 patients in a chronic dialysis program, the treatment of

40,000 patients would require the availability of 2-4,000 physicians for

such an organized effort.  The financial inducement would have to be high

enough to attract this number of physicians to a new type of special

medical activity which, on the whole, appears less attractive to most well-
                                                  

trained men because of the expected limitations and monotony of the treat-

ment of a single,  circumscribed disease condition.


207

The training of specialized paramedical personnel in sufficient

quantities may possibly represent less of a problem although, here too,
we face the spectre of robbing Peter to pay Paul --of withdrawing significant

numbers of veteran nurses from a field of action which is already badly

undermanned at present.

   In either case, acquisition of the necessary new personnel could only
come about very gradually over a period of several years.

  Provided that the necessary funds are available, construction,acquisition
and organization of relevant facilities may not be as forbidding a problem

as that of personnel; here too, however, considerable lead time will be
required until all the necessary facilities would be ready for operation.

  The greatest obstacle to a total push attempt at treating all of the

50,000 yearly patients in chronic progressive renal failure is the medical

nature of this group.  About three-quarters of this group are known to be

above the age of 60.  A large proportion have many other concurrent dis-

orders (chronic heart disease, advanced atherosclerosis, hypertension,

diabetes, and others) which make them poor risks for kidney transplantation

and less than optimal patients for chronic dialysis.  In addition, chronic

dialysis, to be successful, Places large demands on the patient for emotional
stability, and experience has shown that only a portion of those who are
medically suitable for chronic dialysis possess the necessary emotional
(or minimal intellectual) prerequisites.


VI.  FEASIBLE APPROACHES FOR END-STAGE
      KIDNEY DISEASE TREATMENT

The elements for the planning of feasible approaches for end-stage

kidney disease treatment are contained in Chapter 5, which details

hypothetical programs for dealing with the problem of treatment for end-

stage kidney failure.  For the purposes in Chapter 5, the assumption was

made, in these programs, that there had been no problem in recruiting the

necessary medical and paramedical staff, and that the necessary facilities

and funding were available.  Every one of these problems exists, however,
and limits the speed in which either the "intermediate level" or "accelerated

level" programs can be translated into reality. Thus, any feasible program

for the near future must be envisioned within the confines of the following

existing restraints:

  About 6,000 to 8,000 individuals in chronic renal failure are ideally
suited for chronic dialysis.  About a.similar number of patients are assumed

generally to be well suited for kidney transplantation. About 6,000

individuals in each of these groups overlap (i.e. about 2,000 individuals

in each of these groups is ideally suited for one treatment modality but

not for the other).  Most patients suitable for either procedure are

within the 15 to 54 age group.  Since it is self-evident that a number of

years is required for the training and organization of facilities for a

large scale chronic dialysis program, only the most suitable patients can

be considered as serious candidates for such a program in the near future.

In the case of transplantation, the availability of matching kidneys for

the suitable patients in the group of patients maintained by chronic

dialysis will determine the actual number of transplants attempted. Thus

the total number of individuals involved in a program feasible for


activation within the next few years will probably be in the neighborhood
of 8,000 and certainly not more than 10,000.
.For the chronic dialysis component of the program, a conservative
assumption should be made, based on present experience, that in the

beginning about one physician, two nurses and three to four technicians
and aides would be required for every ten patients.  This means that a

going program for 8,000 patients would require 800 specialized physicians,

1600 specially trained nurses, and 4,000 specially trained technicians and

afdes. Because of this heavy demand for personnel the first year of such
a progtam probably could not accommodate more than 800 new patients.
Additional patients would have to be admitted to the program as additional
personnel is trained and becomes available.
  Since it appears that personnel is more of a critical factor than

facilities, the availability of personnel (rather than facilities) is more
likely to govern the number of patients included in this program during

each of the subsequent years.

  To reduce cost to a minimum, and based on experience obtained in
dialysis centers and home dialysis programs thus far, it would probably
be desirable to start new patients in full-time dialysis centers and to
"graduate" subsequently those patients whose personality, family situation
and home conditions are most suitable to home dialysis.  Thus, eventually,
the dialysis centers would harbor at any one time three types of patients:
1) new patients who are being stabilized and trained for home dialysis,
2) patients who have graduated from the center but who have gotten into
trouble during home dialysis and who require, at this point, medically
well supervised treatment, and 3) a hard core of patients who must be


dialyzed in a center setting since they or their family/home conditions

are not conducive to home dialysis, or who have tried home dialysis and

this attempt was not successful in the long run.  In addition, at all times,

each center would harbor a number -of patients on a temporary basis who

are having cannulae placed in their arteries and veins, or whose cannulae

are being declotted, or who are suffering from other intercurrent disorders

or complications.

Since the majority of dialysis patients would also be suitable candidates

for transplantation an attempt would be made to transplant every patient
for whom a matching kidney can be obtained. Thus, each center facility

would embrace both treatment modalities and would consist of a combination

of a chronic dialysis and dialysis training center, and a center for kidney

transplantation and tissue matching activities.  The transplantation staff

would consist primarily of surgical teams and tissue matching laboratory

staff; in addition, the internist/nephrologist staff responsible for the

patients who are being dialyzed will serve for the medical backup of the

transplantation staff.

   With this general framework in mind and utilizing the elements and

computations in Section V. of Chapter 5, it is possible to arrive at s
                      I

practical and feasible predictions concerning the cost of such a program

and the overall number of patients which could be accommodated by it

during each of the first few years, the number of patients who are likely

to graduate from this program permanently each year because of successful

transplantation, the number of individuals who would have to be maintained

permanently with the aid of chronic dialysis, and the number of new patients

which such a program could accommodate each year.


  Assming that the first year could not accommodate more than 800

patients, the subsequent yearly growth of this effort would depend on the

availability of the necessary personnel. Thus, the-number of years required

until such a program could encompass 8,000 top (ideally suitable) candidates

from among the 50,000 new vulnerable individuals each year, will depend on

the availability of the requisite funds, manpower and facilities available

for expansion.