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Chronic Kidney Disease-Related Mineral and Bone Disorder: Public Health Problem Kerry Willis PhD National Kidney Foundation... K/DOQI Clinical Practice Guidelineson Bone Metabolism and D

Chronic Kidney Disease-Related

Mineral and Bone Disorder:

Public Health Problem

Kerry Willis PhD National Kidney Foundation

Year of ESRD Incidence or Transplantation

21.5 19.8

4.1 2.0

1999 annual report of the US Renal Data System

Dialysis All ESRD Cadaveric Transplant Living Related Transplant

Adjusted 1st Year Patient Death Rates by Treatment

Modality and Year of Incidence, 1986-96

100

10 1

Cardiovascular Mortality in the General Population

and in Dialysis Patients

General populationMale

Female

Black White

Dialysis populationMale

Female

Black White

NKF’s Clinical Practice Guidelines

• Evidence Based Review

• Publication and Dissemination

• Implementation

• Reassess Impact

• Update

DOQI K/DOQI KDIGO

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)

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

CKD is a Public Health Problem

• CKD is common

• CKD is harmful

• We have treatment

CKD death

CKD death Complications

Screening for CKD

Diagnosis

& treatment;

Treat comorbid conditions;

Slow progression

Estimate progression;

Treat complications;

Prepare for replacement

Replacement

by dialysis

& transplantNormal Increased Increased risk risk Damage ↓ ↓ GFR GFR Kidney Kidney failure failure

11.3 m 5.6%

7.7 m 3.8%

0.3 m 0.2%

Conceptual Model for CKD

>4.6

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

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/DOQI™ Clinical Practice Guidelines

on Bone Metabolism Target Levels

CKD Stage 3 Stage 4 CKD Stage 5 CKD

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

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)

Smoking Genetics

Dyslipidemia

Carbonyl stress

Low fetuin-A

Traditional Risk Factors Non-traditional Risk Factors

Elevated IL-1, Il-6, TNF α

Homocysteine

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

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

A Framework for Classification of CKD-MBD

Calcification of Vascular or Other Soft Tissue

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

5 New CKD-MBD classification will form the basis for

updated, international clinical practice guidelines

Population Attributable Risk of All

• 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