Naval Submarine

NSMRL REPORT 1183

Medical Research Laboratory

28 DECEMBER 92

ANALYSIS OF KIDNEY STONES IN

THE SUBMARINE FORCE

by

P. L. Perrotta

J. L. Hyashi

and

D. J. Dlugos

Released by

P. K. Weathersby, CAPT, MSC, USN

Commanding Officer

Naval Submarine Medical Research Laboratory

Approved for public release; distribution unlimited
ANALYSIS OF KIDNEY STONES IN

THE SUBMARINE FORCE

by

Peter L. Perrotta, Jennifer L. Hyashi,

and Dennis J. Dlugos

Naval Submarine Medical Research Laboratory

Report 1183

Naval Medical Research and Development Command

Work Unit 63706N M0096.002-5205

Released by

P. K. Weathersby

Commanding Officer

Approved for public release; distribution unlimited
SUMMARY PAGE

PROBLEM:

To retrospectively examine nephrolithiasis waiver and disqualification packages in both the Atlantic and Pacific Submarine Fleets.

FINDINGS:

Medical Officers noted metabolic and environmental conditions predisposing to stone formation

in 53% of the individuals. Hypercalciuria (29%) hyperuricosuria (22%) and hypocitraturia (9%)

were the most frequently documented disturbances. Analysis of individual laboratory values

revealed a greater percentage of abnormalities than noted by Medical Officers. Hypercalciuria

(36%), hyperuricosuria (33%), hyperphosphaturia (32%), hypocitraturia (19%), elevated urinary

sodium (12%), and low urine volume (57%) were the most common laboratory abnormalities.

Individuals with no documented predisposition to stone formation, recurrent stone-formers, submariners with retained stones, and personnel from the Pacific Fleet were less likely to be waived

of physical stnadards (P values < 0.05).

APPLICATION:

Results indicate that the incidence of metabolic abnormalities in the submarine force is greater

than expected and the majority of stone patients have a treatable condition. Personnel with

waivers for nephrolithiasis will need to be followed prospectively over several years to determine additional information (such as recurrence rates with appropriate treatment) and the operational impact of maintaining these individuals' submarine qualifications.

ADMINISTRATIVE INFORMATION

This investigation was conducted under Naval Medical Research Development Command

Research Work Unit 63706N-M0096.002-5205, "Medical conditions affecting submarine

qualifications." The views expressed in this report are those of the authors and do not reflect the

official policy or position of the Department of the Navy, Department of Defense, or the U. S.

Government. This report was approved for publication on

28 December 1992 and designated Naval Submarine Medical Research Report 1183.

ii
Abstract

This report presents the results of a retrospective review of nephrolithiasis waiver and disqualification packages submitted to Atlantic and Pacific Force Medical Officers over the past

three years. General characteristics of stone-formers in the Submarine Force are described. Medical Officers noted metabolic and environmental conditions predisposing to stone formation in

53% of the individuals. Hypercalciuria (29%), hyperuricosuria (22%), and hypocitraturia (9%)

were the most frequently documented disturbances. Analysis of individual laboratory values

revealed a greater percentage of abnormalities than noted by Medical Officers. Hypercalciuria

(36%), hyperuricosuria (33%), hyperphosphaturia (32%), hypocitraturia (29%), elevated urinary

sodium (12%), and low urine volume (57%) were the most common laboratory abnormalities.

Individuals with no documented predisposition to stone formation, recurrent stone-formers, submariners with retained stones, and personnel from the Pacific Fleet were less likely to be waived

of physical stnadards (P values < 0.05). Results indicate that the incidence of metabolic abnormalities in the submarine force is greater than expected and the majority of stone patients have a

treatable abnormality. Personnel with waivers for nephrolithiasis will need to be prospectively

followed over several years to determine additional information (such as recurrence rates with appropriate treatment) and the operational impact of maintaining these indiividuals' submarine

qualifications.

iii
ANALYSIS OF KIDNEY STONES

IN THE SUBMARINE FORCE

Background

Until recently, 40 to 60

submariners were medically

disqualified annually from

submarine duty because of

kidney stones

(nephrolithiasis), resulting in the loss of experienced

individuals to the submarine

force. This policy has

recently been liberalized in

conjunction with a

prospective clinical study

being conducted by the Naval

Submarine Medical Research

Laboratory (NSMRL) and

endorsed by the Chief, Bureau

of Medicine and Surgery (1).

In 1989, Postma and Quinn (2)

rev iewed renal stone waiver

and disqualification packages submitted to Commander

Submarine Force Atlantic

Fleet (COMSUBLANT) during a

16 month period. They found

that the average amount of

experience lost to the

submarine force per disqualification was 8.75

years and concluded that the

policy regarding the

disposition of submariners

with kidney stones should be

liberalized in favor of

medical waiver. This

recommendation was

subsequently endorsed by the

COMSUBLANT Force Medical

Officer in 1989.

The revised guidance (3),

issued in 1990, recommended

that waivers should not be

recommended for those

submariners with retained

stones, recurrent stones,

stones failing to pass

spontaneously, and a solitary

calcareous stone with no

demonstrable treatable

abnormality on standardized

workup (Figure 1). Waivers

could be obtained for first

time stone formers with a

correctable metabolic

abnormality. Correctable

abnormalities would include

environmental conditions such

as dehydration and high

consumption of protein,

sodium, and calcium, and

metabolic abnormalities

resulting in hypercalciuria

or hypocitraturia.

This extensive evaluation for

first-time stone formers was

adapted from several reviews

of the pathogenesis and

treatment of nephrolithiasis

(4,5). Although many

clinicians agree that all

single stone formers should

be evaluated, there is

disagreement on the scope of

the investigation. Wilson

(6) suggested in a recent

review that the initial

evaluation include a medical

history, serum testing for

calcium, phosphorus, uric

acid, and creatinine, an

intravenous pyelogram (IVP)

with tomographic cuts, a

first morning urine pH and

gram stain, and urine culture

if indicated. He did not

recommend performing 24-hour

urine studies as part of the

evaluation. Ryall and

Marshall (7) essentially

agree with this approach.

Preminger (8,9) believes that

an extensive evaluation is

indicated for single stone

formers at "high risk" for

recurrence, a group including

1
Figure 1. Evaluation of Stone Formers in the Submarine Force

Family History of Nephrolithiasis

Dietary History: - Fluid intake, animal protein, drug and vitamin use

Laboratory Data: - Serum Chemistry Panel

- Urinalysis

- Urine Culture (only during acute episode) - 24 Hour Urine calcium x 2, uric acid x 2, sodium x 2,

creatinine x2, oxalate x 1, citrate x 1 and volume x 2

on unrestricted diet - Qualitative urinary cystine - Morning urinary pH for 5 consecutive days - Chemical Analysis of Calculus if available - Calcium fast and load study after 7 day on calcium and

sodium-restricted diet

Radiographic Studies: - Intravenous pyelography

white middle age males with a

family history of stone

disease. His suggested

evaluation includes three 24-

hour urine collections over a

two week period including

tests of urine calcium, uric

acid, citrate, oxalate,

volume, pH, and sodium. A

review by Uribarri (10)

recommends a single 24-hour

urine study measuring

calcium, uric acid, volume,

pH, and citrate for first

time stone formers. Given

the potential operational

impact of an episode of

nephrolithiasis while

underway, medical officers

concede that a rigorous

evaluation of these

individuals is indicated.

There has been considerable

progress in the diagnosis and

treatment of specific

metabolic abnormalities

leading to nephrolithiasis.

Civilian literature has shown

a high incidence of metabolic

abnormalities in single stone

formers, ranging from 50 to

80 percent. Strauss et al.

(11) examined 182 patients

with a single calcium renal

stone and found that 51.1%

had idiopathic hypercalciuria

(elevated urinary calcium

levels not attributed to

known factors such as

increased dietary intake of

calcium or increased renal

excretion of calcium) or

hyperuricosuria and 19.8% had

other systemic disorders

predisposing to stones. Only

29% had no evidence of a

metabolic abnormality in this

2
study. Pak (12) obtained

similar results when

examining 34 patients with a

single episode of stone

formation. Absorptive

hypercalciuria was found in

55.9% (23.5% type I and 32.4%

type II), renal

hypercalciuria in 11.8%,

primary hyperparathyroidism

in 2.9%, hyperuricosuric

calcium oxalate in 8.8% and

no metabolic abnormality in

only 20.6%. These studies

suggest that the majority of

stone formers have an

environmental (e.g.

dehydration, elevated dietary

consumption of calcium) or

physiological disturbance

causing a predisposition to

nephrolithiasis.

Preliminary unpublished data

from the submarine force

indicated that 70-80% of

submariners with renal stones

had normal metabolic

evaluations. It is not known

whether this difference

reflects a different patient

population or a less rigorous

evaluation.

The purpose of this study is

to review the characteristics

of stone disease in the

submarine force over the past

3 years. Incidence of

various metabolic and

environmental abnormalities

will be emphasized.

Methods

One-hundred fifty-two

nephrolithiasis waiver and

disqualification packages

submitted to the Atlantic and

Pacific Force Medical

Officers over approximately 3

years were reviewed. In most

cases, waiver packages are

prepared by either Group or

Squadron medical personnel.

The evaluation is coordinated

by the patients medical

officer and may include

specialty evaluation by a

urologist or other

specialists. Based on the

results of the evaluation,

the medical officer will then

recommend a waiver or

disqualification to the

individual's Commanding

Officer. The Commanding

Officer will then make a

recommendation through the

chain of command which

includes the Force Medical

Officer (COMSUBLANT or

COMSUBPAC) and Chief of the

Bureau of Medicine and

Surgery (BUMED). Waivers are

granted only by Naval

Military Personnel Command

(NMPC). A submariner that is

recommended for waiver of

physical standards by the

local medical officer may be

disqualified at any point in

the chain of command. Only

rarely is a recommendation

for disqualification reversed

by a higher authority.

Cases were excluded if

minimal diagnostic criteria

for nephrolithiasis (typical

renal colic and microscopic

hematuria) were not met or

information in the record

cast doubt on the diagnosis.

Demographic information

(Pacific or Atlantic fleet),

medical history (medications,

concurrent and past medical

illnesses, allergies), family

history of nephrolithiasis,

dietary history, and race

were extracted from the

records if available.

3
Particular attention was

given to the metabolic

evaluation. Results of serum

studies (for electrolytes,

blood urea nitrogen,

creatinine, calcium, uric

acid, and phosphorus), 24-

hour urine samples (for total

volume, calcium, uric acid,

citrate, phosphorus, sodium,

oxalate, and cystine), and

calcium fast and load studies

were recorded. Abnormal

results were based on the

performing laboratory's

reference values. The

clinical interpretation of

the metabolic evaluation by

the medical officer was

noted. Chemical composition

of recovered stones was

recorded. Treatment

protocols initiated as well

as success or failure of

treatments for metabolic

abnormalities were examined.

Data was extracted using

standardized forms and

entered into a database using

Systat 5.0 statistical

software. Categorical

variables were compared using

the chi-square or Fisher

exact test. These tests were

selected to distinguish

significant group differences

between individuals either

waived or disqualified.

Results

General Characteristics

One-hundred thirty-six

packages met established case

criteria for nephrolithiasis.

Characteristics of stoneformers in the submarine

fleet are displayed in Table

1. The mean age of the

subjects at the time of

stone-formation was 29.7

years. One-hundred twentyfour (91%) were enlisted

personnel. Eighty-three

(61%) packages were submitted

from the Atlantic Fleet.

Family history of

nephrolithiasis in a firstdegree relative was present

in 23% when elicited.

Medical evacuation was

necessary in 6 (4.4%) of the

cases, all occurring in first

time stone-formers. A

metabolic abnormality was

noted to be present by the

medical officer in 63 (53% of

cases where this information

was available) of the cases.

Extra corporeal shock wave

lithotripsy or

surgical/cystoscopic removal

of a stone was required in 16

(11.8%) of the cases. For

the group of recurrent stoneformers (13%), the average

time between recurrence was

3.1 years.

4
Table 1. General Characteristics of Stone-Formers in the

Submarine Force

Characteristic Number (%)

Status

Enlisted

Officer

Race

Caucasian

Negroid

Fleet

Atlantic

Pacific

Family History of nephrolithiasis

Number resulting in MEDEVAC

Stone Analysis Available

Retained stone on radiograph

First-time stone former

Documented metabolic abnormality

Cases requiring ESWL

Requiring surgical or cystoscopic removal

Documented anatomic abnormality

Recurrent stone formers

Average time between recurrence, yrs

124 (91)

12 (9)

123 (96)

5 (3.9)

83 (61)

53 (39)

27 (20)

6 (4.4)

41 (30)

9 (8.3)

118 (87)

63 (53)

9 (6.6)

7 (5.2)

7 (5.2)

18 (13)

3.1

Metabolic and Environmental

Risk Factors

Risk factors for stoneformation were reported by

the Medical Officer in 53%

(n=119) of the cases (Table

2).. Hypercalciuria was

present in 29% and

hyperuricosuria in 22% of the

cases. Results are also

reported for the remaining

metabolic (hypocitraturia,

hyperoxaluria) and

environmental (low urine

volume, hyperphosphaturia,

and elevated urinary sodium)

risk factors occurring as

both a sole disturbance and

in combination with other

abnormalities.

5
Table 2. Classification of Nephrolithiasis Risk Factors

By Medical Officers

Total Sole Combined

# (%) Occurrence(%) Occurrence(%)

Hypercalciuria 34 (29) 16 13

Hyperuricosuria 26 (22) 10 12

Hypocitraturia 11 (9) 3 6

Hyperphosphaturia 6 (5) <2 3

Hyperoxaluria 1 (<1) <1 -

Decreased volume 5 (4) 2 2

Elevated Urine Na 3 (3) <1 2

No Abnormality 56 (47) - -

Laboratory Analysis

Results of metabolic

evaluation independent of the

individual medical officer's

interpretation of the

laboratory results are

presented in Table 3. Based

on individual laboratory

reference values, the most

frequently encountered

abnormalities found were

hypercalciuria (36%),

hyperuricosuria (33%), and

hyperphosphaturia (32%).

When urine volume was

standardized to a normal

value of > 1500 ml./day, more

than one-half (57%) of these

measurements were abnormally

low. Hypocitraturia (19%)

and elevated urinary sodium

(12%) were less frequent.

One case of hyperoxaluria was

diagnosed by a physician

based on a borderline urinary

oxalate despite a value

within the normal range. The

one abnormal oxalate value

was disregarded based on a

previously normal value.

Serum calcium and uric acid

were elevated in 3% of

patients tested.

6
Table 3. Laboratory Results on Initial Evaluation

# Tests # Abnormal (%)

Urinary calcium (mg./day) 105 38 (36)

Urinary uric Acid (mg./day) 99 33 (33)

Urinary citrate (mg./day) 63 12 (19)

Urinary phosphorus (mg./day) 44 14 (32)

Urine volume < 15-00 ml./day 106 60 (57)

Urinary sodium (meq/day) 60 7 (12)

Urinary oxalate (mg./day) 69 1 (1)

Urinary cystine (mg./day) 37 5*

Serum uric acid (mg./dl.) 90 3 (3)

Serum calcium (mg./dl.) 102 3 (3)

* Includes 1 positive qualitative test

Waiver -vs- Disqualification

Various characteristics of

submariners waived or

disqualified for

nephrolithiasis were compared

independently (Table 4).

Officers were more likely to

be waived of physical

standards than enlisted

personnel. Significantly

more personnel were

disqualified in the Pacific

Fleet. Although not

statistically significant

because of the small number,

it was noted that no black

submariners were waived.

Those individuals with

treatable metabolic or

environmental abnormalities

were more likely to be waived

than those with no identified

disturbance. No subjects

with retained stones were

waived and recurrent stoneformers were less likely to

be waived. Treatment success

or failure was based on

documented correction of

metabolic or environmental

abnormalities. It was noted

that appropriate medical

treatment of these

abnormalities was usually

successful.

7
Table 2. Classification of Nephrolithiasis Risk Factors

By Medical Officers

Total Sole Combined

# (%) Occurrence(%) Occurrence(%)

Hypercalciuria 34 (29) 16 13

Hyperuricosuria 26 (22) 10 12

Hypocitraturia 11 (9) 3 6

Hyperphosphaturia 6 (5) <2 3

Hyperoxaluria 1 (<1) <1 -

Decreased volume 5 (4) 2 2

Elevated Urine Na 3 (3) <1 2

No Abnormality 56 (47) - -

Laboratory Analysis

Results of metabolic

evaluation independent of the

individual medical officer's

interpretation of the

laboratory results are

presented in Table 3. Based

on individual laboratory

reference values, the most

frequently encountered

abnormalities found were

hypercalciuria (36%),

hyperuricosuria (33%), and

hyperphosphaturia (32%).

When urine volume was

standardized to a normal

value of > 1500 ml./day, more

than one-half (57%) of these

measurements were abnormally

low. Hypocitraturia (19%)

and elevated urinary sodium

(12%) were less frequent.

One case of hyperoxaluria was

diagnosed by a physician

based on a borderline urinary

oxalate despite a value

within the normal range. The

one abnormal oxalate value

was disregarded based on a

previously normal value.

Serum calcium and uric acid

were elevated in 3% of

patients tested.

6
incidence of abnormalities

would likely be greater.

The multiple 24-hour urine

collections required were the

most frequently omitted tests

in these evaluations. The

calcium fast-and-load studies -- currently required in all

cases even if hypercalciuria

is absent -- were not

administered in a

standardized fashion. "Tums"

and "Yogurt", for example,

were used for calcium loading

in some cases, rather than

the standardized 1 gram dose

of calcium mixed in a

synthetic meal recommended in

the original reference (15).

The five day urine pH

measurements were done only

sporadically and performed

with urine dipsticks, rather

than the pH electrode

recommended by other

investigators (16). The time

to complete the entire

evaluation was often greater

than one month, leading to

frustration for both the

practitioner and the

submariner awaiting a

decision on his duty status.

A simplified evaluation would

be welcomed by the Medical

Officers and the submariners

undergoing evaluation.

There were also difficulties

in the interpretation of

laboratory results. These

problems were seen most

commonly with 24-hour urine

studies. As our population

is spread throughout the

United States, Europe, and

Asia, a large number of

military and civilian

laboratories with different

collection standards and

reference values were used.

The "normal" values for 24-

hour urine studies were not

standardized and showed great

variation. Urine volume

values as low as 550 ml. were

not flagged or interpreted as

abnormally low. A number of

abnormal laboratory results

were apparently not felt to

be clinically significant by

Medical Officers. The use of

a single or small group of

reference laboratories

specialized in urine testing

may improve the accuracy of

these tests and lessen

difficulties with the

interpretation of results.

These results suggest that an

extensive, but streamlined,

investigation for metabolic

and environmental

abnormalities predisposing to

nephrolithiasis should be

conducted. Testing for

hypercalciuria,

hyperuricosuria,

hyperphosphaturia,

hypocitraturia, increased

urinary sodium and decreased

urine volume is certainly

warranted, comprising most

abnormalities. Multiple urine

pH measurements (not accurate

unless a pH electrode can be

used) can be replaced by 24-

hour urine pH and citrate

measurements, which will

identify those individuals

with a urine acidification

defect. Oualitative spot

urine testing for cystinuria,

followed by quantitative

measurement of positive test

results, would identify rare

cases of this condition.

The calcium fast and load

tests should be replaced by a

Sodium Cellulose Phosphate

Screening Test (9), which

does not require calcium

loading. This test should

9
Table 4. Characteristics of Waiver and Disqualification

Characteristic Disqualified Waived P Value

Status, n (%)

Enlisted 78 (57) 46 (34) 0.046

Officer 4 (3) 8 (6)

Race, n (I)

White 70 (55) 53 (41)

Black 5 (4)

Fleet, n (%)

Atlantic 41 (30) 42 (31)

Pacific 41 (30) 12 (9) 0.001

Metabolic Abnormality, n(%)

Absent 40 (34) 16 (13) 0.001

Present 25 (21) 38 (32)

Retained Stone, n (#)

No retained stone 51 (47) 49 (45)

Retained stone 9 (8) -

Recurrence, n (%)

First stone 67 (49) 51 (38)

Recurrent stone 15 (11) 3 (2) 0.032

Results of Treatment, n (%)

Not successful 2 (6) 3 (9)

Successful treatment 8 (24) 21 (62)

Discussion

Our study documents a greater

incidence of metabolic and

environmental abnormalities

in submariners with

nephrolithiasis than was

previously estimated by

submarine medical officers.

In fact, the majority of

patients were found to have a

potentially treatable

abnormality. The incidence

of abnormalities, however, is

still considerably lower than

that reported in the civilian

literature where extremely

thorough laboratory

evaluations were conducted

(11,12). One explanation for

this difference is that the

great majority of submarine

evaluations were incomplete

when compared to the

standards used in civilian

studies. Most evaluations

also fell far short of the

Force Medical requirements

(3), although some were

submitted before these

guidelines were disseminated

to all Submarine Medical

Officers. If Medical Officers

were able to complete the

entire evaluation, the

8
5. Coe FL, Parks JH.

Nephrolithiasis:

pathogenesis and

treatment. Second

Edition. Chicago: Year

Book Medical;1988:2.

6. Wilson DM. Clinical and

Laboratory Evaluation of

Renal Stone Patients.

Endocrinology and

Metabolism Clinics of

North America

1990;19:773-803.

7. Ryall RL, Marshall VR.

The Investigation and

Management of Idiopathic

Urolithiasis. In:

Wickham JE, Buck AC,

eds. Renal Tract Stone:

Metabolic Basis and

Clinical Practice.

London:

Churchill;1990:307-331.

8. Preminger GM. The

Metabolic Evaluation of

Patients with Recurrent

Nephrolithiasis: A

Review of Comprehensive

and Simplified

Approaches. Journal of

Urology 1989;141:760-3.

9. Preminger GM, Harvey JA.

Diagnostic

Considerations. In: Pak

CY, ed. Renal Stone

Disease. Boston:

Martinus Nijhoff;

1987:157-60.

10. Uribarri J, Oh MS et al.

The First Kidney Stone.

Annals of Internal

Medicine. 1989;111:1006-

9.

11. Strauss AL, Coe FL,

Parks JH. Formation of

a Single Calcium Stone

of Renal Origin,

Clinical and Laboratory

Characteristics of

Patients. Arch Intern

Med 1982;142:504-507.

12. Pak CY. Should Patients

with Single Renal Stone

Occurrence Undergo

Diagnostic Evaluation?

Journal of Urology

1982;127:855-858.

13. Frank M, et al.

Prevention of

Urolithiasis. Archives

of Environmental Health

1966;13:625-30.

14. Pak CY. Prevention of

Recurrent

Nephrolithiasis. In: Pak

CY, ed. Renal Stone

Disease. Boston:

Martinus

Nijhoff;1987:186-194.

15. Pak CY et al. Ambulatory

Evaluation of

Nephrolithiasis.

American Journal of

Medicine 1980;69:20.

16. Pak CY. Etiology and

Treatment of

Urolithiasis. American

Journal of Kidney

Diseases. 1991; 18:632.

11
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ANALYSIS OF KIDNEY STONES IN THE SUBMARINE FORCE

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P. L. Perrotta, J. L. Hyashi, and D. J. Dlugos

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FIELD GROUP SUB-GROUP ne hrolithiasis, kidney stones, waiver, submarine l:e? sornel

19. ABSTRACT (Continue on reverse if necessary and identify by block number)

This report presents the results of a retrospective review of nephrolithiasis waiver and disqualification packages

submitted to Atlantic and Pacific Force Medical Officers over the past three years. General characteristics of

stone-formers in the submarine force are described. Medical Officers noted metabolic and environmental

conditions predisposing to stone formation in 53% of the individuals. Hypercalciuria (29%), hyperuricosuria

(22%), and hypocitraturia (9%) were the most frequently documented disturbances. Analysis of individual

laboratory values revealed a greater percentage of abnormalities than noted by Medical Officers. Hypercalciuria

(36%), hyperphosphatura (32%), hypocitraturia (19%), elevated urinary sodium (12%), and low urine volume

(57%) were the most common laboratory abnormalities. Individuals with no documented predisposition to stone

formation, recurrent stone-formers, submariners with retained stones, and personnel from the Pacific Fleet were

less likely to be waived of physical standards (p < 0.05). Results indicate that the incidence of metabolic

abnormalities in the submarine force is greater than expected and the majority of stone patients have a treatable

abnormality. Personnel waivers for nephrolithiasis will need to be prospectively followed over several years to

determine additional information (such as recurrence rates with appropriate treatment) and the operational

impact of maintaining these individuals' submarine qualifications.

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