Development of renal disease in people at high cardiovascular risk: results of the HOPE randomized study.

In people with diabetes, renal disease tends to progress from microalbuminuria to clinical proteinuria to renal insuffi- ciency. Little evidence has been published for the nondiabetic population. This study retrospectively analyzed changes of pro- teinuria 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 pro- teinuria (1), and serum creatinine 2.3 mg/dl (200 M). Baseline microalbuminuria predicted subsequent clinical protein- uria 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 partici- pants 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. Microalbumin- uria itself predicts clinical proteinuria in nondiabetic and in dia- betic people. Ramipril prevents or delays the progression of albuminuria. Microalbuminuria is a known risk factor for overt nephrop- athy and subsequent renal insufficiency in people with di- abetes. Estimates of the magnitude of this risk vary widely in people with type 2 diabetes compared with the variation of estimates in people with type 1 diabetes (1,2). The significance of microalbuminuria for renal outcomes in non- diabetic people is even less clear. Indeed, in the latter group, a sequence of events progressing from microalbuminuria to clinical proteinuria and then to subsequent renal insuffi- ciency has not been established. Despite these uncertainties, both nondiabetic and diabetic people at high risk for car- diovascular disease are also at risk for renal insufficiency and renal replacement therapy (3,4). The number of patients with generalized atherosclerosis as well as renal failure is increasing steadily in developed countries (5). We therefore hypothesized that individuals at high risk for cardiovascular disease would also be at high risk for the development of renal disease. The HOPE (Heart Outcomes and Prevention Evaluation) study was a prospective trial including a broad spectrum of people with and without a history of diabetes who were at risk for cardiovascular events (6 -9). People with a serum-creati- nine 2.3 mg/dl (200 mol/L), who had no evidence of clinical proteinuria, were included. The urine albumin/creati- nine ratio was measured at baseline and follow-up in all par- ticipants. This article examines the role of microalbuminuria as a predictor of clinical proteinuria, the development of new microalbuminuria or proteinuria in people without and with diabetes, and the effects of ramipril on these renal outcomes.