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Angiotensin-Receptor Blockers in the Prevention or Treatment of Microalbuminuria
- From Health Sciences Centre, Memorial University, St. John's, Newfoundland A1B 3V6, Canada.
Type 1 and type 2 diabetes mellitus are the most frequent causes of end-stage renal disease in the United States (1). The natural history of diabetic nephropathy starts with microalbuminuria, which may progress to macroalbuminuria, gradual deterioration in glomerular filtration rate (GFR), and eventually end-stage kidney disease. Microalbuminuria in diabetes strongly predicts end-stage renal disease and adverse cardiovascular events (2–4). Although inhibitors of the renin–angiotensin system (RAS) have become the mainstays of treating established diabetic nephropathy (5), the role of these agents in the early phases of diabetic nephropathy is unclear. Kidney damage may occur in diabetics who do not have albuminuria. We do not know whether patients with a high burden of vascular disease but no albuminuria are less likely to develop renal disease if they take RAS-blocking agents. Two articles in this issue examine the effect of angiotensin-receptor blockers (ARBs) on microalbuminuria in 2 different patient groups: diabetics at an early phase of nephropathy (6) and adults with known cardiovascular disease or diabetes with end-organ damage but no albuminuria at baseline (7).
Bilous and colleagues (6) used data from the DIRECT (Diabetic Retinopathy Candesartan Trials) randomized trials to examine the effect of candesartan on microalbuminuria and albumin excretion rates, either before renal disease began or in its earliest stages. The primary outcome in these 3 related studies was retinopathy, and the studies were powered to determine whether candesartan could prevent the development of diabetic retinopathy in type 1 diabetes (n = 1421) or the progression of mild to moderate retinopathy in type 1 diabetes (n = 1905) or type 2 diabetes (n = 1905) (8–10). The median follow-up was 4.7 years. The incidence of microalbuminuria in the pooled sample (n = 5234) was a prespecified primary end point. Because type 1 and type …
