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

USRDS, 2000 Incidence/Prevalence of ESRD in the US

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 m 2 ), elevated urinary albumin to creatinine ratio (ACR; mg/g) and gender. Coresh et al, JASN 16: , 2005

Cockcroft-Gault Equation 1 MDRD Equation 2 GFR(ml/min/1.73m 2 )= 170 (S cr ) (Age) (SUN) (Alb) (0.762 if female)(1.180 if black) 72(S cr ) (0.85 if female) (140-Age)(Weight) C cr (ml/min)= 1 Cockcroft and Gault, Nephron Levey et al, Ann Intern Med 1999 Estimating GFR

Modified MDRD equation –e-GFR = 186 x (P CR ) x (Age) x (0.742 if female) x (1.210 if African American) Convince the lab to do it automatically On-line e-GFR calculators – _adults.htmhttp:// _adults.htm – cfmhttp:// cfm

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

Sample e-GFR Serum Creatinine AgeMaleFemale 1.2 mg/dl mg/dl

Chronic Kidney Disease progression risks Hypertension Proteinuria Glycemic control Smoking Lipids

CKD Progression Risks hypertension

CKD Progression Risks proteinuria

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 Sep;12(9):

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

GFR Time ACEi/ARB

ACEi/ARB and GFR Heart Rate GFR  -Blocker ACEi/ARB

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

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. – Chronic Kidney Disease management

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 Jun;65(6): ) 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 Walker JD et al, Lancet 2:1411, 1989 Zeller K et al, N Engl J Med 324:78, 1991

II. Managing complications of CKD Anemia Diagnosis of exclusion Check iron stores –TSAT (iron/TIBC) 20-50% –Ferritin ng/ml Erythropoietin replacement therapy Goal Hg g/dL

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

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

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 1 st encounter with nephrologist within 1 year of RRT 32% had 1 st appt < 4 months before ESRD Patients referred late ( 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