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

Chronic Kidney Disease-Related Mineral and Bone Disorder: Public Health Problem. Kerry Willis PhD National Kidney Foundation. 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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Chronic Kidney Disease-Related Mineral and Bone Disorder: Public Health Problem

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  1. Chronic Kidney Disease-Related Mineral and Bone Disorder:Public Health Problem Kerry Willis PhD National Kidney Foundation

  2. Dialysis All ESRD Cadaveric Transplant Living Related Transplant 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

  3. Cardiovascular Mortality in the General Population and in Dialysis Patients General population Dialysis population Male Black Male Black Female Female White White 100 10 1 Annual mortality (%) 0.1 0.01 25–34 35–44 45–54 55–64 65–74 75–84 85 Age (years)

  4. NKF’s Clinical Practice Guidelines • Evidence Based Review • Publication and Dissemination • Implementation • Reassess Impact • Update

  5. 1997 1999 2005 DOQI K/DOQI KDIGO 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

  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

  7. KDOQI: CKD Staging

  8. CKD is a Public Health Problem • CKD is common • CKD is harmful • We have treatment

  9. 7.7 m 11.3 m 5.6% 7.7 m 3.8% 0.3 m 0.2% Conceptual Model for CKD Complications Normal Increasedrisk Damage  GFR Kidneyfailure CKDdeath Screening for CKDrisk factors: diabeteshypertension age >60family history US ethnic minorities CKD riskreduction;Screening forCKD Diagnosis& treatment;Treat comorbidconditions;Slow progression Estimateprogression;Treatcomplications;Prepare forreplacement Replacementby dialysis& transplant

  10. >4.6

  11. K/DOQI Clinical Practice Guidelineson Bone Metabolism and Diseasein Chronic Kidney Disease Published October 2003

  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

  13. K/DOQI™ Clinical Practice Guidelineson Bone Metabolism Target Levels *Evidence

  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

  15. 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 < 10.2 mg/dL (2.55 mmol/L); Ca X P < 55 mg2/dL2

  16. Homocysteine 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

  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 increasedmorbidity/mortalityof abnormal serum biochemistries (i.e. phosphorus), nor increased awareness of vascular disease related to bone and mineral disorders in CKD patients.

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

  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. Kidney International June 2006

  22. www.kdigo.org

  23. 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

  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 Block et al JASN 2004

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