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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 All ESRD Cadaveric Transplant Living Related Transplant Deaths/100 patient-years Dialysis 21.5 19.8 4.1 2.0 Year of ESRD Incidence or Transplantation 1999 annual report of the US Renal Data System Cardiovascular Mortality in the General Population and in Dialysis Patients General population Male Female Dialysis population Black White Male Female Black White Annual mortality (%) 100 10 0.1 0.01 25–34 35–44 45–54 55–64 65–74 Age (years) 75–84 ≥85 NKF’s Clinical Practice Guidelines • Evidence Based Review • Publication and Dissemination • Implementation • Reassess Impact • Update 1997 DOQI Dialysis Anemia Access *updates 1999 2005 K/DOQI KDIGO Nutrition (00) Hep C (’08) Dialysis (’01)* Bone/Mineral (’08) Anemia (’01)* Access(‘01)* CKD class (’02) Bone/Mineral (’03) Lipids (’03) Htn (’04) CV (’05) Diabetes (’07) http://www.kidney.org/professionals/kdoqi 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: 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 GFR 60 family history US ethnic minorities Increased risk CKD risk reduction; Screening for CKD 11.3 m 5.6% 7.7 m m 7.7 3.8% 0.3 m 0.2% Damage Damage ↓↓ GFR GFR Kidney Kidney failure Diagnosis & treatment; Treat comorbid conditions; Slow progression Estimate progression; Treat complications; Prepare for replacement Replacement by dialysis & transplant CKD CKD death >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 Chair: Shaul G Massry, MD KECK School of Medicine Vice-Chair: Jack W Coburn, MD VA Greater Los Angeles Work Group Members: Glenn M Chertow, MD, MPH University of California, San Francisco James T McCarthy, MD Mayo Clinic Keith Hruska, MD Barnes Jewish Hospital Sharon Moe, MD Indiana University Craig Langman, MD Children’s Memorial Hospital Isidro B Salusky, MD UCLA School of Medicine Hartmut Malluche, MD University of Kentucky Donald J Sherrard, MD VA Puget Sound Kevin Martin, MD, BCh St Louis University Miroslaw Smogorzewski, MD University of Southern California Linda M McCann, RD, CSR, LD Satellite Dialysis Centers Kline Bolton, MD RPA Liaison K/DOQI™ Clinical Practice Guidelines on Bone Metabolism Target Levels P (mg/dL) CKD Stage CKD Stage CKD Stage (on dialysis) 2.7 - 4.6 2.7 - 4.6 3.5 - 5.5* Ca (mg/dL) “Normal” “Normal” Intact PTH (pg/mL) 35 - 70 70 - 110 *Evidence 8.4 - 9.5; Hypercalcemia = >10.2 150 - 300* Treatment Recommendations (Stages & 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 Treatment Recommendations Stage (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 < 10.2 mg/dL (2.55 mmol/L); Ca X P < 55 mg2/dL2 Traditional Risk Factors Smoking Non-traditional Risk Factors Diabetes Elevated IL-1, Il-6, TNFα Genetics Oxidation (OxLDL) HTN Homocysteine Advanced glycation end-products Age Dyslipidemia Fractures Cardiovascular disease in CKD Abnormal bone Carbonyl stress Low fetuin-A Abnormal mineral metabolism 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 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 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
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