Albuminuria, a therapeutic target for cardiovascular protection in type 2 diabetic patients with nephropathy

Background - Albuminuria is an established risk marker for both cardiovascular and renal outcomes. Albuminuria can be reduced with drugs that block the renin-angiotensin system (RAS). We questioned whether the short-term drug-induced change in albuminuria would predict the long-term cardioprotective efficacy of RAS intervention. Methods and Results - We analyzed data from Reduction in Endpoints in Non - insulin dependent diabetes mellitus with the Angiotensin II Antagonist Losartan (RENAAL), a double-blind, randomized trial in 1513 type 2 diabetic patients with nephropathy, focusing on the relationship between the prespecified cardiovascular end point ( composite) or hospitalization for heart failure and baseline or reduction in albuminuria. Patients with high baseline albuminuria (greater than or equal to3 g/g creatinine) had a 1.92-fold (95% CI, 1.54 to 2.38) higher risk for the cardiovascular end point and a 2.70-fold ( 95% CI, 1.94 to 3.75) higher risk for heart failure compared with patients with low albuminuria (< 1.5 g/g). Among all available baseline risk markers, albuminuria was the strongest predictor of cardiovascular outcome. The association between albuminuria and cardiovascular outcome was driven by those patients who also had a renal event. Modeling of the initial 6-month change in risk parameters showed that albuminuria reduction was the only predictor for cardiovascular outcome: 18% reduction in cardiovascular risk for every 50% reduction in albuminuria and a 27% reduction in heart failure risk for every 50% reduction in albuminuria. Conclusions - Albuminuria is an important factor predicting cardiovascular risk in patients with type 2 diabetic nephropathy. Reducing albuminuria in the first 6 months appears to afford cardiovascular protection in these patients.