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Development of Renal Disease in People at High Cardiovascular Risk: Results of the HOPE Randomized Study

Johannes F. E. Mann, Hertzel C. Gerstein, Qi-Long Yi, Eva M. Lonn, Byron J. Hoogwerf^*, Andrew Rashkow^* and Salim Yusuf on behalf of the HOPE investigators

*Department of Cardiology and Population Health Research Institute, McMaster University, Hamilton, Canada; Schwabing General Hospital, Ludwig Maximilians University Munich, Germany; and German Institute for High Blood Pressure Research, Heidelberg, Germany.

Correspondence to: HOPE Office, McMaster University, Hamilton General Hospital, 237 Barton Street East, Hamilton, ONT L8L 2X2 Canada. Phone: 905-527-4322; Fax: 905-521-1166;

ABSTRACT. In people with diabetes, renal disease tends to progress from microalbuminuria to clinical proteinuria to renal insufficiency. Little evidence has been published for the nondiabetic population. This study retrospectively analyzed changes of proteinuria over 4.5 yr in the HOPE (Heart Outcomes and Prevention Evaluation) study, which compared ramipril’s effects to placebo in 9297 participants, including 3577 with diabetes and 1956 with microalbuminuria. This report is restricted to 7674 participants with albuminuria data at baseline and at follow-up. Inclusion criteria were known vascular disease or diabetes plus one other cardiovascular risk factor, exclusion criteria included heart failure or known impaired left ventricular function, dipstick-positive proteinuria (>1+), and serum creatinine >2.3 mg/dl (200 µM). Baseline microalbuminuria predicted subsequent clinical proteinuria for the study participants overall (adjusted odds ratio [OR], 17.5; 95% confidence interval [CI], 12.6 to 24.4), in participants without diabetes (OR, 16.7; 95% CI, 8.6 to 32.4), and in participants with diabetes (OR, 18.2; 95% CI, 12.4 to 26.7). Any progression of albuminuria (defined as new microalbuminuria or new clinical proteinuria) occurred in 1859 participants; 1542 developed new microalbuminuria, and 317 participants developed clinical proteinuria. Ramipril reduced the risk for any progression (OR, 0.87; 95% CI, 0.78 to 0.97; P = 0.0146). People without and with diabetes who are at high risk for cardiovascular disease are also at risk for a progressive rise in albuminuria. Microalbuminuria itself predicts clinical proteinuria in nondiabetic and in diabetic people. Ramipril prevents or delays the progression of albuminuria. E-mail: johannes.mann@kms.mhn.de

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Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673