# Presentation: 859276

## Chronic Kidney Disease-Related Mineral and Bone Disorder:Public Health Problem

- Kerry Willis PhD
- National Kidney Foundation

## Adjusted 1st Year Patient Death Rates by Treatment Modality and Year of Incidence, 1986-96

**Year of ESRD Incidence or Transplantation**

**21.5**

**19.8**

**4.1**

**2.0**

**1999 annual report of the US Renal Data System**

**Deaths/100 patient-years**

## Cardiovascular Mortality in the General Population and in Dialysis Patients

**0.01**

**100**

**10**

**1**

**0.1**

**Annual mortality (%)**

**25–34**

**45–54**

**65–74**

******85**

**35–44**

**55–64**

**75–84**

**Age (years)**

**General population**

**Male **

**Female**

**Black**

**White**

**Dialysis population**

**Male **

**Female**

**Black**

**White**

##  NKF’s Clinical Practice Guidelines

-  Evidence Based Review
-  Publication and Dissemination
-  Implementation
-  Reassess Impact
-  Update

## DOQI

**DOQI**

**KDIGO**

**K/DOQI**

- Dialysis
- Anemia
- Access

- Nutrition (00)
- Dialysis (’01)*
- Anemia (’01)*
- Access(‘01)*
- CKD class. (’02)
- Bone/Mineral (’03)
- Lipids (’03)
- Htn (’04)
- CV (’05)
- Diabetes (’07)

- Hep C (’08)
- Bone/Mineral (’08)

**1997**

**2005**

- *updates

- http://www.kidney.org/professionals/kdoqi

**1999**

- http://www.kdigo.org/welcome.htm

## NKF-K/DOQI Definition of CKD

- Structural or functional abnormalities of the kidneys for _>_3 months, as manifested by either:
- 1. **Kidney damage**, with or without decreased GFR, as defined by
- pathologic abnormalities
**markers of kidney damage**
- urinary abnormalities (**proteinuria**)
- blood abnormalities (renal tubular syndromes)
- imaging abnormalities
- kidney transplantation
- 2. **GFR <60 ml/min/1.73 m****2**, with or without kidney damage

## KDOQI: CKD Staging

| Stage | Description | GFR (ml/min/1.73 m2) |
| --- | --- | --- |
| 1 | Kidney damage with normal or  GFR |  90 |
| 2 | Kidney damage with mild  GFR | 60-89 |
| 3 | Moderate  GFR | 30-59 |
| 4 | Severe  GFR
 | 15-29 |
| 5 | Kidney failure | < 15 (or dialysis) |

## CKD is a Public Health Problem 

**CKD is common**
**CKD is harmful**
**We have treatment**

## Conceptual Model for CKD

**Complications**

**Screening ****for CKD****risk factors:**
**diabetes****hypertension**
**age >60****family history**
**US ethnic minorities**

**CKD risk****reduction;****Screening for****CKD**

**Diagnosis****& treatment;****Treat ****comorbid****conditions;****Slow ****progression**

**Estimate****progression;****Treat****complications;****Prepare for****replacement**

**Replacement****by dialysis****& transplant**

**Normal**

**Increased****risk**

**Kidney****failure**

**Damage**

****** ****GFR**

## Slide 10

## K/DOQI Clinical Practice Guidelineson Bone Metabolism and Diseasein Chronic Kidney Disease

- Published October 2003

## KDOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease

***Chair:******	******	******	******	******	******Vice-Chair:***
**Shaul G. Massry, MD****	****	****	****	****Jack W. Coburn, MD**
**KECK School of Medicine****	****	****	****VA Greater Los Angeles**
*** ***
***Work Group Members:***
**Glenn M. Chertow, MD, MPH****	****	****	****James T. McCarthy, MD**
**University of California, San Francisco****	****	****Mayo Clinic**
**	**
**Keith Hruska, MD****	****	****	****	****Sharon Moe, MD**
**Barnes Jewish Hospital****	****	****	****Indiana University**
**Craig Langman, MD****	****	****	****	****Isidro B. Salusky, MD**
**Children’s Memorial Hospital****	****	****	****UCLA School of Medicine**
**Hartmut Malluche, MD****	****	****	****Donald J. Sherrard, MD**
**University of Kentucky****	****	****	****VA Puget Sound**
**Kevin Martin, MD, BCh****	****	****	****Miroslaw Smogorzewski, MD**
**St. Louis University****	****	****	****	****University of Southern California**
**	**
**Linda M. McCann, RD, CSR, LD****	****	****	****Kline Bolton, MD**
**Satellite Dialysis Centers****	****	****	****RPA Liaison**

## K/DOQITM Clinical Practice Guidelineson Bone Metabolism  Target Levels

|  | CKD 
Stage 3 | CKD 
Stage 4 | CKD 
Stage 5
(on dialysis) |
| --- | --- | --- | --- |
| P
(mg/dL) | 2.7 - 4.6 | 2.7 - 4.6 | 3.5 - 5.5* |
| Ca
(mg/dL) | “Normal” | “Normal” | 8.4 - 9.5; 
Hypercalcemia = >10.2
 |
| Intact PTH
(pg/mL) | 35 - 70 | 70 - 110 | 150 - 300*
 |

- *Evidence

## Treatment Recommendations(Stages 3 & 4)

- Decrease total body phosphorus burden by dietary restriction and phosphorus binder therapy- 2.7- 4.6 mg/dL; *begin when EITHER elevated serum phosphorus OR elevated serum PTH*
- Treat elevated PTH with active oral vitamin D sterol to target of 35-70 (CKD 3) or 70-110 (CKD 4) pg/mL by intact assay
- Normalize serum calcium

## Normalize serum phosphorus by diet and phosphorus binder therapy- 3.5-5.5 mg/dL (1.13 -1.78 mmol/L); limit elemental calcium intake from binders to 1500 mg/day
Treat elevated PTH with active vitamin D sterol to target of 150-300 pg/mL (16-32 pmol/L) by intact assay
Normalize serum calcium- ideally 8.4 -9.5 mg/dL (2.10-2.38 mmol/L), and always < 10.2 mg/dL (2.55 mmol/L); Ca X P < 55 mg2/dL2

- Treat elevated PTH with active vitamin D sterol to target of **150-300 pg/mL (16-32 pmol/L) by intact assay**
- Normalize serum calcium- ideally **8.4 -9.5 mg/dL (2.10-2.38 mmol/L), and always < 10.2 mg/dL (2.55 mmol/L); Ca X P < 55 mg****2****/dL****2**

**Treatment Recommendations****Stage 5 (dialysis)**

## Cardiovascular disease in CKD

**Age**

**Oxidation (OxLDL)**

**Diabetes**

**HTN**

**Advanced glycation**
** ****end-products**

**Smoking**

**Genetics**

**Dyslipidemia**

**Carbonyl stress**

**Low fetuin-A**

_**Traditional Risk Factors**_

_**Non-traditional Risk Factors**_

**Elevated IL-1, Il-6, TNF******

**Abnormal mineral metabolism**

**Fractures**

**Cardiovascular disease in CKD**

## Classification Issues in Bone and Mineral Disorders

- The term renal osteodystrophy is used to describe different entities
- The predominant use is to describe a disorder of bone remodeling.  However this does not take into account new data that there is increased morbidity/mortality of abnormal serum biochemistries (i.e. phosphorus), nor increased awareness of vascular disease related to bone and mineral disorders in CKD patients.

## Definition, Evaluation and Classification 

**Definition, Evaluation and Classification **
**of Renal Osteodystrophy:**
***A position statement from Kidney Disease ***
***Improving Global Outcomes *****(KDIGO)**
**April, 2006**

## Standardization of Terms

- The term renal osteodystrophy (ROD)* *should be used exclusively to define the bone pathology associated with CKD.
- The clinical, biochemical, and imaging abnormalities should be defined more broadly as a clinical entity or syndrome called Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD).

## Definition of CKD-MBD

- 	A systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following:
- Abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism
- Abnormalities in bone turnover, mineralization, volume, linear growth, or strength
- Vascular or other soft tissue calcification

-  Moe et al Kidney International June 2006

## Kidney International June 2006

| A Framework for Classification of CKD-MBD |  |  |  |
| --- | --- | --- | --- |
| Type* | Laboratory
Abnormalities | Bone Disease | Calcification of Vascular or Other Soft Tissue |
| L | + | - | - |
| LB | + | + | - |
| LC | + | - | + |
| LBC | + | + | + |
|    * L = laboratory abnormalities (of calcium, phosphorus, PTH, alkaline phosphatase or vitamin D metabolism);  B = bone disease (abnormalities in bone turnover, mineralization, volume, linear growth, or strength);  C = calcification of vascular or other soft tissue.
 |  |  |  |

*Kidney International June 2006*

## www.kdigo.org

## Summary

- CKD is defined using eGFR and classified into 5 stages
- This classification can help predict clinical outcomes
- Early detection and treatment can improve patient outcomes
- There is a link between CVD and bone and mineral disease in CKD
- New CKD-MBD classification will form the basis for
- 	updated, international clinical practice guidelines

## Population Attributable Risk of All Cause Mortality in CKD 5D

- 17.5%	Mineral metabolism abnormalities 			(Phosphorus > 5.0 mg/dl, Calcium > 10 		mg/dl, intact PTH > 600 pg/ml)
- 11.3%	Anemia (hgb < 11 g/dl)
- 5.1%	Inefficient Dialysis (URR < 65%)
- Corollary:  We should be able to significantly improve mortality of CKD patients by improving control of mineral metabolism

**Block et al JASN 2004**