www.usrds.org www.usrds.org 1

1,749 + (2,032) 1,563 to <1,749 1,414 to <1,563 1,283 to <1,414 Below 1,283 (1,178) December 31 point prevalent ESRD patients. By HSA; rates adjusted for age, gender, and race. Excludes patients residing in Puerto Rico and the Territories. Number of Patients (in thousands) 300 250 200 150 100 50 Incidence Other Diabetes 0 1980 1990 2000 2010 2020 2030 1,500 Prevalence 1,250 1,000 750 500 250 Other Diabetes 0 1980 1990 2000 2010 2020 2030 www.usrds.org. Diabetes mellitus Hypertension Glomerulonephritis IgA nephropathy Minimal change/membranous/fsgs 2

About 15% of the U.S. population has CKD Most CKD patients die of heart disease before reaching ESRD About 547,000 patients on dialysis or with a kidney transplant About 382,000 dialysis; 165,000 transplant Death rates are 20% per year for dialysis population and the number of end-stage patients rises about 1 3% each year Medicare spent 26.8 billion dollars in 2008, which is 5.9% of the Medicare budget www.usrds.org Glomerular filtration rate Albuminuria/proteinuria (140 age) Weight (kg) X X 0.85 (if female) Serum Cr 72 3

Many doctors might think her GFR is about 60 70 ml/min (140 70) 55 X 1.5 72 X 0.85 (for a female) = 30.3 ml/min Estimated GFR (ml/min/1.73m 2 ) = 186 x (scr) 1.154 x (Age) 0.203 x (0.742 if female) x (1.210 if African American) = exp(5.228 1.154xln(SCr) 0.203 x In(Age) (0.299 if female) + (0.192 if African American) Cockcroft-Gault Formula Creatinine Clearance Estimated Clearance = (140 age/serum Cr) x wt (kg)/72 x (0.85 if female) Complications of renal disease (e.g., anemia, renal osteodystrophy, malnutrition, and volume regulatory disorders) are seen with increasing frequency at Stage 3 kidney disease (GFR <60 ml/min) Deleterious relationship between chronic kidney disease and cardiovascular disease Risk for contrast dye nephropathy Drug dose adjustments 4

Poor correlation to actual GFR when GFR is greater than 60 ml/min Not accurate for acute renal failure Nor is any GFR estimate CKD-EPI formula appears to be more accurate for GFR >60 ml/min Normal renal excretion is about 200 300 mg/day of total protein (up to 20 mg is albumin) Single specimen urine albumin/creatinine ratio Normal <30 mg/g Microalbuminuria 30 300 mg/g Macroalbuminuria >300 mg/g Schwab SJ et al. Arch Int Med. 1987;83:405-410. 5

6 5 4 Relative Risk 3 of IHD 2 General Population Normoalbuminuria Microalbuminuria 1 0 10-y follow-up, n = 2085 Female Male Borch-Johnsen K et al. Arterioscler Thromb Vasc Biol. 1999;19:1992-1997. Ninomiya T et al. J Am Soc Nephrol. 2009;20:1813-1819. 6

A1C of <7% Blood pressure control <130/80 mm Hg Lower urine albumin level Dietary interventions as indicated Low salt intake for hypertension control No role for low-protein diet Stop smoking Writing Team for the DCCT. JAMA. 2003;290:2159-2167. 7

Pickering TG et al. Hypertension. 2008;52:1-9 Primary hyperaldosteronism Renal artery stenosis 8

Umpierrez GE et al. Diabetes Care. 2007;30:1699-1703. Diagnose angiography with contrast dye Angiography with radiocontrast dye Magnetic resonance angiography with gadolinium Duplex ultrasound Dye is potentially toxic to the kidney Prehydration with IV 1/2 normal saline lowers incidence of acute renal failure Surgical intervention usually does not improve outcomes compared with medical management 9

ASTRAL Investigators. N Engl J Med. 2009;361:1953-1962. <130/80 mm Hg 10

NKF-KDOQI Guidelines. Intensive BP 118/75 Moderate BP 124/80 Estacio RO et al. Am J Hypertens. 2006;19:1241-1248. 11

BP = Cardiac Output x Total Peripheral Resistance Heart Rate x Stroke Volume blockers Salt Restriction Diuretics (e.g., thiazides) Natriuretics (e.g., ANP, BNP) Aquaretics (AVP Rec. Antagonist) Aldosterone Antagonist Calcium Channel Blockers Dihydropyridines Nondihydropyridines Angiotensin II Inhibitors Renin Inhibitor Central Adrenergic Agonists Alpha Blockers Nitric Oxide Enhancers It doesn t matter Because 3 or more drugs are usually needed Target other associated diseases Recent myocardial infarction Congestive heart failure Kidney disease Although an ACE inhibitor is a reasonable first choice, as there is evidence of activated RAAS in diabetes 12

Mauer MM et al. N Engl J Med. 2009,;61:40-51. ACE inhibitors and/or angiotensin receptor blockers should be administered to patients with increased urine albumin/protein even with normal blood pressure Placebo Captopril Lewis EJ et al. N Engl J Med. 1993;329:1456-1462. 13

coe.fgcu.edu/.../greenep/kidney/glomerulus.html. Holtkamp FA et al. Kidney Int. 2011;80:282-287. Jennings DL et al. Diabet Med. 2007;24:486-493. 14

ONTARGET Investigators. N Engl J Med. 2008;358:1547-1549. Current evidence: All patients with increased urine albumin (or total protein) should be on an ACE inhibitor or angiotensin receptor blocker, even if the patient has excellent blood pressure Avoid combination of ACE-I and ARB in patients with normal kidney function and no increase in urine albumin/protein level Use combination in patients with kidney disease to decrease high urine albumin/proteinuria levels 15

Postgraduate Med. 2009. Parving HH et al. N Engl J Med. 2008;358:2433-2446. Postgraduate Med. 2009. 16

Schrier RW et al. Clin J Amer Soc Nephrol. 2010;5:1132-1140. Mehdi UF et al. J Amer Soc Nephrol. 2009;20:26412650. 17

DCA NDCA Bakris GL et al. Kidney Int. 2004;65:1991-2002. McCormick BB et al. Am J Kidney Dis. 2008;52:454-463. Difficult-to-control hypertension Hypertension management questions Questions about managing RAAS inhibitors Questions about treatment of albuminuria Worsening renal function Unexplained urinalysis findings (e.g., proteinuria, hematuria) Questions about diagnosis Questions about diagnosis or management of disorders of electrolytes, acid-base, calcium/phosphate, and anemia, especially in patients with chronic kidney disease 18

Measure serum creatinine and use MDRD or CKD-EPI formula to estimate GFR Measure urine albumin/creatinine ratio in spot urine specimen Cardiac evaluation as indicated A1C <7% Blood pressure control <130/80 mm Hg Lower urine albumin level RAAS blockade/blood glucose control/hypertension control Dietary interventions as indicated Low salt intake for hypertension control No role for low-protein diet Stop smoking 19