Comment on: Hellemons et al. 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. Diabetes Care 2011;34:2078-2083.

Hellemons et al. (1) in a post hoc analysis of the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria (IRMA)-2 trial provocatively showed that the initial reduction of microalbumiuria with an angiotensin receptor blocker (ARB) was independently associated with renoprotection (i.e., independent of blood pressure changes). Antihypertensive medication was removed for a 3-week run-in period before the ARB was (re)introduced. If these results could be confirmed in a randomized controlled trial (RCT) it would imply that aggressive reduction of microalbuminuria should be attempted—an approach not currently recommended by the American Diabetes Association (2). This might be a difficult goal to accomplish clinically given the marked day-to-day intraindividual variability (33–61%) of microalbuminuria (3,4). We could not lower established microalbuminuria in an RCT pilot study in patients already treated with submaximal doses of an ACE inhibitor by maximizing the doses of a combination of benazepril plus losartan compared with 10 mg of the ACE inhibitor over a mean of 12 months (5). In our run-in period, patients were kept on 10 mg of benazepril. This might be an important factor in designing future real-world RCTs to test the hypothesis generated by the post hoc analysis of the IRMA-2 trial (1).