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  1. 1. Chronic Kidney Disease-Related Mineral and Bone Disorder: Public Health Problem Kerry Willis PhD National Kidney Foundation
  2. 2. 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
  3. 3. 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
  4. 4. NKF’s Clinical Practice Guidelines <ul><li>Evidence Based Review </li></ul><ul><li>Publication and Dissemination </li></ul><ul><li>Implementation </li></ul><ul><li>Reassess Impact </li></ul><ul><li>Update </li></ul>
  5. 5. 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
  6. 6. NKF-K/DOQI Definition of CKD <ul><li>Structural or functional abnormalities of the kidneys for > 3 months, as manifested by either: </li></ul><ul><li>1. Kidney damage , with or without decreased GFR, as defined by </li></ul><ul><ul><ul><li>pathologic abnormalities </li></ul></ul></ul><ul><ul><ul><li>markers of kidney damage </li></ul></ul></ul><ul><ul><ul><ul><li>urinary abnormalities ( proteinuria ) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>blood abnormalities (renal tubular syndromes) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>imaging abnormalities </li></ul></ul></ul></ul><ul><ul><ul><li>kidney transplantation </li></ul></ul></ul><ul><li>2. GFR <60 ml/min/1.73 m 2 , with or without kidney damage </li></ul>
  7. 7. 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
  8. 8. CKD is a Public Health Problem <ul><li>CKD is common </li></ul><ul><li>CKD is harmful </li></ul><ul><li>We have treatment </li></ul>
  9. 9. 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%
  10. 10. >4.6
  11. 11. K/DOQI Clinical Practice Guidelines on Bone Metabolism and Disease in Chronic Kidney Disease Published October 2003
  12. 12. KDOQI Clinical Practice Guidelines for Bone Metabolism and Disease in Chronic Kidney Disease <ul><li>Chair: Vice-Chair: </li></ul><ul><li>Shaul G. Massry, MD Jack W. Coburn, MD </li></ul><ul><li>KECK School of Medicine VA Greater Los Angeles </li></ul><ul><li>Work Group Members: </li></ul><ul><li>Glenn M. Chertow, MD, MPH James T. McCarthy, MD </li></ul><ul><li>University of California, San Francisco Mayo Clinic </li></ul><ul><li>Keith Hruska, MD Sharon Moe, MD </li></ul><ul><li>Barnes Jewish Hospital Indiana University </li></ul><ul><li>Craig Langman, MD Isidro B. Salusky, MD </li></ul><ul><li>Children’s Memorial Hospital UCLA School of Medicine </li></ul><ul><li>Hartmut Malluche, MD Donald J. Sherrard, MD </li></ul><ul><li>University of Kentucky VA Puget Sound </li></ul><ul><li>Kevin Martin, MD, BCh Miroslaw Smogorzewski, MD </li></ul><ul><li>St. Louis University University of Southern California </li></ul><ul><li>Linda M. McCann, RD, CSR, LD Kline Bolton, MD </li></ul><ul><li>Satellite Dialysis Centers RPA Liaison </li></ul>
  13. 13. 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
  14. 14. Treatment Recommendations (Stages 3 & 4) <ul><li>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 </li></ul><ul><li>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 </li></ul><ul><li>Normalize serum calcium </li></ul>
  15. 15. <ul><li>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 </li></ul><ul><li>Treat elevated PTH with active vitamin D sterol to target of 150-300 pg/mL (16-32 pmol/L) by intact assay </li></ul><ul><li>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 </li></ul>Treatment Recommendations Stage 5 (dialysis)
  16. 16. 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
  17. 17. Classification Issues in Bone and Mineral Disorders <ul><li>The term renal osteodystrophy is used to describe different entities </li></ul><ul><li>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. </li></ul>
  18. 18. Definition, Evaluation and Classification of Renal Osteodystrophy: A position statement from Kidney Disease Improving Global Outcomes (KDIGO) April, 2006
  19. 19. Standardization of Terms <ul><li>The term renal osteodystrophy (ROD) should be used exclusively to define the bone pathology associated with CKD. </li></ul><ul><li>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) . </li></ul>
  20. 20. Definition of CKD-MBD <ul><li>A systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of the following: </li></ul><ul><ul><li>Abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism </li></ul></ul><ul><ul><li>Abnormalities in bone turnover, mineralization, volume, linear growth, or strength </li></ul></ul><ul><ul><li>Vascular or other soft tissue calcification </li></ul></ul>Moe et al Kidney International June 2006
  21. 21. 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
  22. 22. www.kdigo.org
  23. 23. Summary <ul><li>CKD is defined using eGFR and classified into 5 stages </li></ul><ul><li>This classification can help predict clinical outcomes </li></ul><ul><li>Early detection and treatment can improve patient outcomes </li></ul><ul><li>There is a link between CVD and bone and mineral disease in CKD </li></ul><ul><li>New CKD-MBD classification will form the basis for </li></ul><ul><li>updated, international clinical practice guidelines </li></ul>
  24. 24. Population Attributable Risk of All Cause Mortality in CKD 5D <ul><li>17.5% Mineral metabolism abnormalities (Phosphorus > 5.0 mg/dl, Calcium > 10 mg/dl, intact PTH > 600 pg/ml) </li></ul><ul><li>11.3% Anemia (hgb < 11 g/dl) </li></ul><ul><li>5.1% Inefficient Dialysis (URR < 65%) </li></ul><ul><li>Corollary: We should be able to significantly improve mortality of CKD patients by improving control of mineral metabolism </li></ul>Block et al JASN 2004