Disease related mineral and bone disorder
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Disease-Related Mineral and Bone Disorder
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Disease related mineral and bone disorder
- 1. Chronic Kidney Disease-Related Mineral and Bone Disorder: Public Health Problem Kerry Willis PhD National Kidney Foundation Brought to you by
- 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 Brought to you by
- 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 Brought to you by
- 4. NKF’s Clinical Practice Guidelines • Evidence Based Review • Publication and Dissemination • Implementation • Reassess Impact • Update Brought to you by
- 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 Brought to you by
- 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 Brought to you by
- 8. CKD is a Public Health Problem • CKD is common • CKD is harmful • We have treatment Brought to you by
- 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 Brought to you by
- 10. KI (2007) 71, 31-38. Levin et. al. Prevalence of Abnormal Mineral Metabolism in CKD >4.6 Brought to you by
- 11. K/DOQI Clinical Practice Guidelines on Bone Metabolism and Disease in Chronic Kidney Disease Published October 2003 Brought to you by
- 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 Brought to you by
- 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 Brought to you by
- 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) Brought to you by
- 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 Brought to you by
- 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. Brought to you by
- 18. Definition, Evaluation and Classification of Renal Osteodystrophy: A position statement from Kidney Disease Improving Global Outcomes (KDIGO) April, 2006 Brought to you by
- 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
- 22. Brought to you by
- 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 Brought to you by
- 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