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

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Chronic Kidney Disease-Related Mineral and Bone
DisorderPublic Health Problem

• Kerry Willis PhD
• National Kidney Foundation

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Adjusted 1st Year Patient Death Rates by
Treatment Modality and Year of Incidence, 1986-96
Deaths/100 patient-years
21.5
19.8
4.1
2.0
Year of ESRD Incidence or Transplantation
1999 annual report of the US Renal Data System
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Cardiovascular Mortality in the General
Population and in Dialysis Patients
General population
Dialysis population
Male
Black
Male
Black
Female
White
Female
White
100
10
1
Annual mortality ()
0.1
0.01
2534
4554
6574
?85
3544
5564
7584
Age (years)
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NKFs Clinical Practice Guidelines

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

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1997
2005
1999
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)
updates
http//www.kidney.org/professionals/kdoqi
http//www.kdigo.org/welcome.htm
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NKF-K/DOQI Definition of CKD

• Structural or functional abnormalities of the
  kidneys for gt3 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 lt60 ml/min/1.73 m2, with or without kidney
  damage

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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 lt 15 (or dialysis)
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CKD is a Public Health Problem

• CKD is common
• CKD is harmful
• We have treatment

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Conceptual Model for CKD
Complications
CKDdeath
Normal
Increasedrisk
Kidneyfailure
Damage
? GFR
Screening for CKDrisk factors diabeteshyperten
sion age gt60family history US ethnic minorities
CKD riskreductionScreening forCKD
Diagnosis treatmentTreat comorbidconditions
Slow progression
EstimateprogressionTreatcomplicationsPrepare
forreplacement
Replacementby dialysis transplant
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K/DOQI Clinical Practice Guidelineson Bone
Metabolism and Diseasein Chronic Kidney Disease

• Published October 2003

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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
• Childrens 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

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K/DOQI Clinical Practice Guidelineson 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 gt10.2
Intact PTH (pg/mL) 35 - 70 70 - 110 150 - 300
Evidence
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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

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Treatment RecommendationsStage 5 (dialysis)

• 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 lt 10.2 mg/dL (2.55
  mmol/L) Ca X P lt 55 mg2/dL2

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Traditional Risk Factors
Non-traditional Risk Factors
Diabetes
Elevated IL-1, Il-6, TNFa
Smoking
Genetics
Oxidation (OxLDL)
HTN
Advanced glycation end-products
Age
Dyslipidemia
Carbonyl stress
Cardiovascular disease in CKD
Fractures
Low fetuin-A
Abnormal bone
Abnormal mineral metabolism
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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.

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

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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
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A Framework for Classification of CKD-MBD A Framework for Classification of CKD-MBD A Framework for Classification of CKD-MBD 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. 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. 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. 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
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www.kdigo.org
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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

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Population Attributable Risk of All Cause
Mortality in CKD 5D

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

Block et al JASN 2004