CLINICAL RESEARCH

Lowering Blood Pressure Reduces Renal Events in Type 2 Diabetes

Bastiaan E. de Galan ^*, Vlado Perkovic ^*1, Toshiharu Ninomiya ^*, Avinesh Pillai ^*, Anushka Patel ^*, Alan Cass ^*, Bruce Neal ^*, Neil Poulter , Stephen Harrap , Carl-Erik Mogensen ^||, Mark Cooper ^¶, Michel Marre ^**, Bryan Williams , Pavel Hamet , Giuseppe Mancia , Mark Woodward ^*, Paul Glasziou ^||||, Diederick E. Grobbee ^¶¶, Stephen MacMahon ^*, John Chalmers ^*, and on behalf of the ADVANCE Collaborative Group

*George Institute For International Health, University of Sydney, Sydney, Australia; Department of General Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands; International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, United Kingdom; Department of Physiology, University of Melbourne, Melbourne Australia; ||Medical Department M, Aarhus University Hospital, Aarhus Sygehus, Aarhus C, Denmark; ¶Danielle Alberti Memorial Centre for Diabetes Complications, Baker Heart Research Institute, Melbourne, Australia; **Service d’Endocrinologie Diabétologie Nutrition, Groupe Hospitalier Bichat–Claude Bernard, Paris, France; Department of Cardiovascular Sciences, University of Leicester School of Medicine, Leicester, United Kingdom; Research Centre, Centre hospitalier de l’Université de Montréal (CHUM), Montreal, Québec, Canada; Department of Clinical Medicine and Prevention, University of Milano-Bicocca, Milan, Italy; ||||Centre for Evidence-Based Practice, Institute of Health Sciences, Oxford University, Oxford, United Kingdom; and ¶¶Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, Netherlands

¹ To whom correspondence should be addressed. E-mail: vperkovic{at}george.org.au.

	Abstract

BP is an important determinant of kidney disease among patients with diabetes. The recommended thresholds to initiate treatment to lower BP are 130/80 and 125/75 mmHg for people with diabetes and nephropathy, respectively. We sought to determine the effects of lowering BP below these currently recommended thresholds on renal outcomes among 11,140 patients who had type 2 diabetes and participated in the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study. Patients were randomly assigned to fixed combination perindopril-indapamide or placebo, regardless of their BP at entry. During a mean follow-up of 4.3 yr, active treatment reduced the risk for renal events by 21% (P < 0.0001), which was driven by reduced risks for developing microalbuminuria and macroalbuminuria (both P < 0.003). Effects of active treatment were consistent across subgroups defined by baseline systolic or diastolic BP. Lower systolic BP levels during follow-up, even to <110 mmHg, was associated with progressively lower rates of renal events. In conclusion, BP-lowering treatment with perindopril-indapamide administered routinely to individuals with type 2 diabetes provides important renoprotection, even among those with initial BP <120/70 mmHg. We could not identify a BP threshold below which renal benefit is lost.