Disease-Related Mineral and Bone Disorder

1. Chronic Kidney Disease-Related
Mineral and Bone Disorder:
Public Health Problem
Kerry Willis PhD
National Kidney Foundation
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2. 0
5
10
15
20
25
30
35
1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996
Year of ESRD Incidence or Transplantation
21.5
19.8
4.1
2.0
1999 annual report of the US Renal Data System
Deaths/100patient
Dialysis All ESRD Cadaveric Transplant Living Related Transplant
Adjusted 1st Year Patient Death Rates by Treatment
Modality and Year of Incidence, 1986-96
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3. 0.01
100
10
1
0.1
Annualmortality(%)
25–34 45–54 65–74 ≥8535–44 55–64 75–84
Age (years)
Cardiovascular Mortality in the General Population
and in Dialysis Patients
General population
Male
Female
Black
White
Dialysis population
Male
Female
Black
White
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4. NKF’s Clinical Practice Guidelines
• Evidence Based Review
• Publication and Dissemination
• Implementation
• Reassess Impact
• Update
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5. DOQI KDIGOK/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
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6. 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 m2
, with or without kidney
damage Brought to you by

7. 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)
KDOQI: CKD Staging
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8. CKD is a Public Health Problem
• CKD is common
• CKD is harmful
• We have treatment
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9. CKDCKD
deathdeath
CKDCKD
deathdeath
ComplicationsComplicationsComplicationsComplications
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
NormalNormalNormalNormal
IncreasedIncreased
riskrisk
IncreasedIncreased
riskrisk
KidneyKidney
failurefailure
KidneyKidney
failurefailure
DamageDamageDamageDamage ↓↓ GFRGFR↓↓ GFRGFR
11.3 m11.3 m
5.6%5.6%
7.7 m7.7 m7.7 m7.7 m
3.8%3.8%
0.3 m0.3 m
0.2%0.2%
Conceptual Model for CKD
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10. KI (2007) 71, 31-38. Levin et. al.
Prevalence of Abnormal Mineral Metabolism in CKD
>4.6
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11. K/DOQI Clinical Practice Guidelines
on Bone Metabolism and Disease
in Chronic Kidney Disease
Published October 2003
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12. 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
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13. K/DOQI™ 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 Brought to you by

14. 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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15. • 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
Treatment Recommendations
Stage 5 (dialysis)
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16. Abnormal boneAbnormal bone
AgeAge
Oxidation (OxLDL)Oxidation (OxLDL)
DiabetesDiabetes
HTNHTN
Advanced glycationAdvanced glycation
end-productsend-products
SmokingSmoking
GeneticsGenetics
DyslipidemiaDyslipidemia
Carbonyl stressCarbonyl stress
Low fetuin-ALow fetuin-A
Traditional Risk Factors Non-traditional Risk Factors
Elevated IL-1, Il-6, TNFElevated IL-1, Il-6, TNFαα
HomocysteineHomocysteine
Abnormal mineral metabolismAbnormal mineral metabolism
FracturesFractures
CardiovascularCardiovascular
disease in CKDdisease in CKD
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17. 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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18. Definition, Evaluation and Classification
of Renal Osteodystrophy:
A position statement from Kidney Disease
Improving Global Outcomes (KDIGO)
April, 2006
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19. 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).

20. 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

21. 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

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23. Summary
1. CKD is defined using eGFR and classified into 5
stages
2. This classification can help predict clinical outcomes
3. Early detection and treatment can improve patient
outcomes
4. There is a link between CVD and bone and mineral
disease in CKD
5. New CKD-MBD classification will form the basis for
updated, international clinical practice guidelines
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24. 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 Brought to you by

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