A very interesting study which explores the role of angiotensin receptor blocking treatment in preventing diabetic nephropathy in normotensive and normoalbuminuric patients. The benefits of early introduction of ACEI/ARB treatment in slowing progression of nephropathy in albuminuric patients has already been established but the investigators of this study conclude that such treatment has no benefit in preventing biopsy proven nephropathy in normoalbuminuric patients.
Renal and Retinal Effects of Enalapril and Losartan in Type 1 Diabetes. Michael Mauer, M.D., Bernard Zinman, M.D., Robert Gardiner, M.D., Samy Suissa, Ph.D., Alan Sinaiko, M.D., Trudy Strand, R.N., Keith Drummond, M.D., Sandra Donnelly, M.D., Paul Goodyer, M.D., Marie Claire Gubler, M.D., and Ronald Klein, M.D., M.P.H. N Engl J Med 2009 361: 40-51
Background Nephropathy and retinopathy remain important complications of type 1 diabetes. It is unclear whether their progression is slowed by early administration of drugs that block the renin–angiotensin system.
Methods We conducted a multicenter, controlled trial involving 285 normotensive patients with type 1 diabetes and normoalbuminuria and who were randomly assigned to receive losartan (100 mg daily), enalapril (20 mg daily), or placebo and followed for 5 years. The primary end point was a change in the fraction of glomerular volume occupied by mesangium in kidney-biopsy specimens. The retinopathy end point was a progression on a retinopathy severity scale of two steps or more. Intention-to-treat analysis was performed with the use of linear regression and logistic-regression models.
Results A total of 90% and 82% of patients had complete renal-biopsy and retinopathy data, respectively. Change in mesangial fractional volume per glomerulus over the 5-year period did not differ significantly between the placebo group (0.016 units) and the enalapril group (0.005, P=0.38) or the losartan group (0.026, P=0.26), nor were there significant treatment benefits for other biopsy-assessed renal structural variables. The 5-year cumulative incidence of microalbuminuria was 6% in the placebo group; the incidence was higher with losartan (17%, P=0.01 by the log-rank test) but not with enalapril (4%, P=0.96 by the log-rank test). As compared with placebo, the odds of retinopathy progression by two steps or more was reduced by 65% with enalapril (odds ratio, 0.35; 95% confidence interval [CI], 0.14 to 0.85) and by 70% with losartan (odds ratio, 0.30; 95% CI, 0.12 to 0.73), independently of changes in blood pressure. There were three biopsy-related serious adverse events that completely resolved. Chronic cough occurred in 12 patients receiving enalapril, 6 receiving losartan, and 4 receiving placebo.
Conclusions Early blockade of the renin–angiotensin system in patients with type 1 diabetes did not slow nephropathy progression but slowed the progression of retinopathy.