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  • 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 Deaths/100 patient-years Adjusted 1st Year Patient Death Rates by Treatment Modality and Year of Incidence, 1986-96 Dialysis All ESRD Cadaveric Transplant Living Related Transplant
  • 0.01 100 10 1 0.1 Annual mortality (%) 25–34 45–54 65–74  85 35–44 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
  • NKF’s Clinical Practice Guidelines
    • Evidence Based Review
    • Publication and Dissemination
    • Implementation
    • Reassess Impact
    • Update
  • 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) 1997 2005 *updates http://www.kidney.org/professionals/kdoqi 1999 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:
    • 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
  • KDOQI: CKD Staging < 15 (or dialysis) Kidney failure 5 15-29 Severe  GFR 4 30-59 Moderate  GFR 3 60-89 Kidney damage with mild  GFR 2  90 Kidney damage with normal or  GFR 1 GFR (ml/min/1.73 m 2 ) Description Stage
  • CKD is a Public Health Problem
    • CKD is common
    • CKD is harmful
    • We have treatment
  • CKD death Complications 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 Normal Increased risk Kidney failure Damage  GFR Conceptual Model for CKD 11.3 m 5.6% 7.7 m 7.7 m 3.8% 0.3 m 0.2%
  • >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: 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
  • K/DOQI™ Clinical Practice Guidelines on Bone Metabolism Target Levels *Evidence 35 - 70 “ Normal” 2.7 - 4.6 CKD Stage 3 150 - 300* 70 - 110 Intact PTH (pg/mL) 8.4 - 9.5; Hypercalcemia = >10.2 “ Normal” Ca (mg/dL) 3.5 - 5.5* 2.7 - 4.6 P (mg/dL) CKD Stage 5 (on dialysis) CKD Stage 4
  • 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
    • 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 mg 2 /dL 2
    Treatment Recommendations Stage 5 (dialysis)
  • Abnormal bone Age Oxidation (OxLDL) Diabetes HTN Advanced glycation end-products Smoking Genetics Dyslipidemia Carbonyl stress Low fetuin-A Traditional Risk Factors Non-traditional Risk Factors Elevated IL-1, Il-6, TNF  Abnormal mineral metabolism Fractures Cardiovascular disease in CKD Homocysteine
  • 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
  • Kidney International June 2006 * 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. + + + LBC + - + LC - + + LB - - + L Calcification of Vascular or Other Soft Tissue Bone Disease Laboratory Abnormalities Type* A Framework for Classification of CKD-MBD
  • www.kdigo.org
  • 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
  • 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