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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 Incidence/Prevalence of ESRD in the US USRDS, 2000 Trivedi et al, AJKD 39: 721-9, 2002 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 Estimating GFR • Cockcroft-Gault Equation1 Ccr(ml/min)= (140-Age)(Weight) 72(Scr) (0.85 if female) • 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) 1 Cockcroft and Gault, Nephron 1976 2 Levey et al, Ann Intern Med 1999 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 CKD Staging K/DOQI guidelines, AJKD, Vol. 39, No 2, Suppl 1, February 2002 Sample e-GFR Serum Creatinine 1.2 mg/dl 2.0 mg/dl Age Male Female 35 73 54 70 64 47 35 41 30 70 35 26 Chronic Kidney Disease progression risks • • • • • Hypertension Proteinuria Glycemic control Smoking Lipids CKD Progression Risks hypertension CKD Progression Risks proteinuria U protein on Ccr 0 -2 0 2 4 6 8 10 -2 -4 Slope ml/min/y -6 -8 All MAP -10 Norm BP Hi BP -12 -14 -16 -18 -20 U protein; g/d 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. 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 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. CKD Progression Risks lipids Samuelsson O et al, Nephrol Dial Transplant. 1997 Sep;12(9):1908-15 ACE Inhibitors and CKD Progression Meta-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 ACEi/ARB 100 GFR 80 60 40 20 0 Time ACEi/ARB and GFR 60 50 80 40 60 30 40 20 20 10 0 0 b-Blocker ACEi/ARB GFR Heart Rate 100 Chronic Kidney Disease management I. Slow the progression • Blood pressure • Smoking • Proteinuria • Lipids • Protein restriction • Glycemic control II. Evaluate and treat complications • Anemia • Osteodystrophy III. Prepare for renal replacement therapy • Vascular access • Referral to Nephrology 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 I. Slowing the progression of CKD Hypertension 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? 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) Protein Restriction (0.6 gm/kg) and DM Nephropathy Change GFR (mL/min/month) 0 Walker Zeller -0.2 -0.4 Control Low -0.6 -0.8 -1 -1.2 Walker JD et al, Zeller K et al, N Engl Lancet 2:1411, 1989 J Med 324:78, 1991 II. Managing complications of CKD Anemia • 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 II. Managing complications of CKD Osteodystrophy • 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 II. Managing complications of CKD Osteodystrophy II. Managing complications of CKD Osteodystrophy • Dietary phosphate restriction • Phosphate binders – Calcium carbonate, Calcium Acetate – Lanthanum Carbonate – Sevalamer • 1,25 Vitamin D • Calcimimetic- not approved for pre-ESRD III. Preparing for RRT Vascular 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 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 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