Clinical Science Articles Impact of Blood Pressure Control and Angiotensin- Converting Enzyme Inhibitor Therapy on New-Onset Microalbuminuria in Type 2 Diabetes: A Post Hoc Analysis of the BENEDICT Trial Piero Ruggenenti,* † Annalisa Perna,* Maria Ganeva,* Bogdan Ene-Iordache,* and Giuseppe Remuzzi;* † for the BENEDICT Study Group *Clinical Research Center for Rare Diseases “Aldo & Cele Dacco `,” Mario Negri Institute for Pharmacological Research, and † Unit of Nephrology, Azienda Ospedaliera Ospedali Riuniti, Bergamo, Italy For assessment of the independent renoprotective effect of BP control and angiotensin-converting enzyme inhibitor (ACEi) therapy, the relationships of baseline BP, BP reduction, and follow-up BP with the incidence of persistent microalbuminuria were evaluated in 1204 hypertensive patients who had type 2 diabetes and normoalbuminuria and were included in the BErgamo Nephrologic Diabetic Complications Trial (BENEDICT) study and were randomly assigned to 3.6 yr of treatment with the ACEi trandolapril (2 mg/d), the nondihydropyridine calcium channel blocker (ndCCB) verapamil SR (240 mg/d), their fixed combination Veratran (trandolapril 2 mg/d plus verapamil SR 180 mg/d), or placebo, plus other antihypertensive medications targeted at systolic/diastolic BP <130/80 mmHg. Follow-up (from month 3 to study end) systolic, diastolic, mean, and pulse BP and their reductions versus baseline— but not baseline BP—independently predicted (P < 0.001) the risk for microalbuminuria. In patients with follow-up BP above medians, ACEi significantly reduced the risk for microalbuminuria to levels that were observed among patients with BP below medians, regardless of ACEi treatment. The same trend was observed among patients with BP reductions below medians. ndCCB therapy did not independently affect microalbuminuria. Patients who were on Veratran had lower BP and less frequently received diuretics,  blockers, or dihydropyridine dCCB. In hypertensive, normoalbuminuric patients with type 2 diabetes, BP reduction and ACEi therapy both independently may prevent microalbuminuria. ACEi therapy is particularly effective when BP is poorly controlled, whereas ndCCB therapy is ineffective at any level of achieved BP. As compared with trandolapril, Veratran may help with achievement of target BP with less need for concomitant antihypertensive medications. J Am Soc Nephrol 17: 3472–3481, 2006. doi: 10.1681/ASN.2006060560 P atients with type 2 diabetes and hypertension have a seven-fold greater risk for progressing to ESRD and a two- to four-fold greater risk for developing cardiovas- cular sequelae, such as myocardial infarction, stroke, or death, as compared with age-matched control subjects and with pa- tients with type 2 diabetes but normal BP (1,2). In patients who had type 2 diabetes and overt nephropathy and were enrolled in the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study and in the Irbesartan Diabetic Nephropathy Trial (IDNT), there was a significant relationship between the BP levels that were achieved during the follow-up period and the incidence of ESRD or cardiovas- cular events (3,4). Although at any level of achieved BP the overall incidence of events was consistently lower in patients on angiotensin II receptor blocker (ARB) than in those who were on placebo treatment, it also was apparent that the impact of achieved BP on clinical outcomes was independent of patient allocation to ARB or placebo treatment and was consistent within each treatment group (5). In patients with type 2 diabe- tes and established nephropathy, both renin-angiotensin-sys- tem (RAS) inhibition and BP control have specific and probably additive reno- and cardioprotective effects that may contribute to limit the excess renal and cardiovascular risk via different pathways. Whether this applies also to patients with type 2 diabetes but still no evidence of renal disease is not established so far. The Bergamo Nephrologic Diabetic Complications Trial (BENEDICT) found that in patients with type 2 diabetes, arte- rial hypertension, and normoalbuminuria, angiotensin-convert- ing-enzyme inhibitor (ACEi) therapy with trandolapril plus verapamil or trandolapril alone delayed the onset of microalbu- minuria, which is a major risk factor for renal and cardiovas- cular events in this population (6). Finding that this effect was significant even after adjustments for baseline and follow-up systolic (SBP) and diastolic BP (DBP) provided the evidence of Received June 5, 2006. Accepted September 13, 2006. Published online ahead of print. Publication date available at www.jasn.org. Address correspondence to: Dr. Piero Ruggenenti, “Mario Negri” Institute for Pharmacological Research, Negri Bergamo Laboratories, Via Gavazzeni, 11-24125 Bergamo, Italy. Phone: +39-035-319-888; Fax: +39-035-319-331; E-mail: manuelap@marionegri.it Copyright © 2006 by the American Society of Nephrology ISSN: 1046-6673/1712-3472