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New Concepts in Chronic Kidney Disease

New Concepts in Chronic Kidney Disease. Jonathan B. Jaffery, MD Assistant Professor of Medicine University of Wisconsin-Madison. New Concepts in Chronic Kidney Disease. The Epidemic Estimating GFR & Staging Risk factors for progression Role of Angiotensin II Management.

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New Concepts in Chronic Kidney Disease

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  1. New Concepts in Chronic Kidney Disease Jonathan B. Jaffery, MD Assistant Professor of Medicine University of Wisconsin-Madison

  2. New Concepts in Chronic Kidney Disease • The Epidemic • Estimating GFR & Staging • Risk factors for progression • Role of Angiotensin II • Management

  3. Incidence/Prevalence of ESRD in the US USRDS, 2000

  4. Trivedi et al, AJKD 39: 721-9, 2002

  5. Patient awareness of CKD Proportion of individuals who were ever told that they had weak or failing kidneys by the level of GFR (ml/min per 1.73 m2), elevated urinary albumin to creatinine ratio (ACR; mg/g) and gender. Coresh et al, JASN 16: 180-188, 2005

  6. Estimating GFR • Cockcroft-Gault Equation1 • MDRD Equation2 GFR(ml/min/1.73m2)= 170 (Scr)-0.999(Age)-0.176(SUN)-0.170(Alb)+0.318 (0.762 if female)(1.180 if black) (140-Age)(Weight) Ccr(ml/min)= (0.85 if female) 72(Scr) 1 Cockcroft and Gault, Nephron 1976 2 Levey et al, Ann Intern Med 1999

  7. Estimating GFR • Modified MDRD equation • e-GFR = 186 x (PCR)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if African American) • Convince the lab to do it automatically • On-line e-GFR calculators • http://www.nkdep.nih.gov/healthprofessionals/tools/gfr_adults.htm • http://www.kidney.org/kls/professionals/gfr_calculator.cfm

  8. CKD Staging K/DOQI guidelines, AJKD, Vol. 39, No 2, Suppl 1, February 2002

  9. Sample e-GFR

  10. Chronic Kidney Diseaseprogression risks • Hypertension • Proteinuria • Glycemic control • Smoking • Lipids

  11. CKD Progression Riskshypertension

  12. CKD Progression Risks proteinuria

  13. Measuring proteinuria • The ratio of protein or albumin to creatinine in an untimed (spot) urine sample is an accurate alternative to measurement of protein excretion in a 24-hour urine collection.

  14. CKD Progression Risks glycemic control Cumulative Incidence of Urinary Albumin Excretion {300 mg per 24 Hours (Dashed Line) and 40 mg per 24 Hours (Solid Line)} in Patients with IDDM Receiving Intensive or Conventional Therapy. Diabetes Control and Complications Trial Research Group, N Engl J Med 329:977, 1993

  15. CKD Progression Risks smoking Mean calculated glomerular filtration rate (GFR) at each year after study entry during the 5-year follow-up in smokers (—•—) versus nonsmokers (—     —) with established diabetic nephropathy. *P < 0.03 versus nonsmokers.

  16. CKD Progression Risks lipids • Samuelsson O et al, Nephrol Dial Transplant. 1997 Sep;12(9):1908-15

  17. ACE Inhibitors and CKD ProgressionMeta-analysis • 11 randomized controlled trials comparing ACE inhibitors vs. other medications in treatment of hypertension in 1860 nondiabetic patients with CKD (S Cr=2.3). • Results: • ACE inhibitors lowered BP and proteinuria. • ACE inhibitors decreased the combined risk of progression of CKD and development of ESRD by 30%, independent of BP lowering effects. Jafar T, Ann Intern Med 135:73-87, 2001

  18. ACEi/ARB 100 GFR 80 60 40 20 0 Time

  19. ACEi/ARB and GFR 60 100 Heart Rate 50 80 40 GFR 60 30 40 20 20 10 0 0 b-Blocker ACEi/ARB

  20. Slow the progression • Blood pressure • Smoking • Proteinuria• Lipids • Protein restriction • Glycemic control Evaluate and treat complications • Anemia • Osteodystrophy Prepare for renal replacement therapy • Vascular access • Referral to Nephrology Chronic Kidney Disease management

  21. Chronic Kidney Disease management • National Kidney Foundation Kidney Disease Outcome Quality Initiative (K/DOQI) • The Kidney Disease Outcomes Quality Initiative or K/DOQI provides evidence-based clinical practice guidelines developed by volunteer physicians and health care providers for all stages of chronic kidney disease and related complications, from diagnosis to monitoring and management. • http://www.kidney.org/professionals/kdoqi/index.cfm

  22. I. Slowing the progression of CKD Hypertension

  23. I. Slowing the progression of CKD Proteinuria • ACEi or ARB • Nondihydropyridine calcium channel blockers (verapamil and diltiazem) • have been shown to effective in reducing urinary albumin excretion, beyond ability to lower blood pressure (Bakris GL et al, Kidney Int. 2004 Jun;65(6): 1991-2002) • Combinations?

  24. I. Slowing the progression of CKD Protein Restriction • Animal studies - dietary protein restriction significantly slows development of renal disease • MDRD Study • 585 nondiabetic patients with GFR 39 ml/min randomized to either 1.1 or 0.7 gm protein/kg/day • Results – Reduction of protein intake minimally ameliorated decline of GFR (1.1 cc/min/year)

  25. Protein Restriction (0.6 gm/kg) and DM Nephropathy Zeller K et al, N Engl J Med 324:78, 1991 Walker JD et al, Lancet 2:1411, 1989

  26. II. Managing complications of CKDAnemia • Diagnosis of exclusion • Check iron stores • TSAT (iron/TIBC) 20-50% • Ferritin 100-600 ng/ml • Erythropoietin replacement therapy • Goal Hg 11-12 g/dL

  27. II. Managing complications of CKDOsteodystrophy • High-turnover (osteitis fibrosa cystica) bone disease • Low-turnover (adynamic) bone disease • Resistance to PTH • Need for relatively higher PTH levels to maintain adequate bone remodeling • Low-turnover may have worse outcomes than high • Check phosphorous, calcium, intact PTH

  28. II. Managing complications of CKDOsteodystrophy

  29. II. Managing complications of CKDOsteodystrophy • Dietary phosphate restriction • Phosphate binders • Calcium carbonate, Calcium Acetate • Lanthanum Carbonate • Sevalamer • 1,25 Vitamin D • Calcimimetic- not approved for pre-ESRD

  30. III. Preparing for RRTVascular access • Goal is to: • Increase use of fistulas • Avoid use of tunneled catheters • Save the Veins! • Avoid blood draws/IVs in non-dominant arm • NO subclavian central lines

  31. III. Preparing for RRT Referral • > 50% of patients had 1st encounter with nephrologist within 1 year of RRT • 32% had 1st appt < 4 months before ESRD • Patients referred late (< 4 months before ESRD) had 72% greater mortality during the first year of HD compared with patients referred early (> 4 months before ESRD) Stack AG, AJKD February 2003

  32. Chronic Kidney Disease summary • CKD- common final pathway • Stage using MDRD equation • Use spot urine protein:creatinine ratio • Goal is: • Prevention • Slow progression of disease • Prevent and manage complications • Control of proteinuria & blood pressure • RAAS inhibition • Early referral to nephrology

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