Initial Angiotensin Receptor Blockade-Induced Decrease in Albuminuria Is Associated With Long-Term Renal Outcome in Type 2 Diabetic Patients With Microalbuminuria A post hoc analysis of the IRMA-2 trial

OBJECTIVE-We aimed to investigate the individual impact of initial responses in urinary albumin excretion (UAE) and systolic blood pressure (SBP) to angiotensin II receptor blocker (ARB) treatment on long-term renal outcome in patients with type 2 diabetes and microalbuminuria. RESEARCH DESIGN AND METHODS-In a post hoc analysis of the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA)-2 trial we first assessed the individual variability in UAE and SBP response (0-6 months) in 531 subjects. Subsequently, we analyzed the individual effect of both response parameters on renal outcome defined as change in estimated glomerular filtration rate (eGFR) during 2 years of follow-up. RESULTS-The median reductions in UAE and SBP in the population were -18% and -11 mmHg, respectively. In irbesartan-treated patients, 85 (24.4%) had a robust (>median) reduction in UAE but not in SBP (discordant SBP response) and 67 (19.3%) had a robust (>median) reduction in SBP but not in UAE (discordant UAE response). The degree of reduction in UAE was independently associated with the rate of eGFR decline (P = 0.0037). SBP showed a similar trend (P = 0.087). The relation between a larger UAE reduction and a slower rate of renal function decline was present in both cohorts with a SBP change above and below the median. CONCLUSIONS-Within an individual, UAE response to ARB therapy may be discordant from SBP response. The initial change in UAE was independently associated with eGFR slope; the more UAE reduction the less eGFR decline, irrespective of the SBP change. These results suggest that in microalbuminuric patients with type 2 diabetes, UAE should be monitored after initiation of therapy and a separate target for renoprotective therapy. Diabetes Care 34:2078-2083,2011