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【NEJM】早期阻断RAS系统并不能延缓T1D肾病的进展
Diabetic nephropathy, responsible for more than 45% of cases of end-stage renal disease in the United States,1 may be structurally advanced once albuminuria becomes detectable.2,3 Blockers of the renin–angiotensin system are more effective than other antihypertensive agents in slowing nephropathy progression in patients who have proteinuria, diabetes mellitus, and a reduced glomerular filtration rate (GFR),4,5,6 and such blockers can also decrease proteinuria in patients with diabetes.7 Although the reduction of proteinuria in patients with diabetes has been associated with a reduction in the rate of decline in GFR in small studies,8 this association has not been systematically tested; in addition, proteinuria reduction is not a generally accepted surrogate for hard clinical end points such as end-stage renal disease.9 Intensive multifactorial intervention in patients with type 2 diabetes with microalbuminuria nearly halved the progression of proteinuria but did not alter the rate of GFR decline.10,11
In the Renin–Angiotensin System Study (RASS), we asked whether blockade of the renin–angiotensin system before the onset of albuminuria in patients with type 1 diabetes could slow progression of the early histologic lesions of diabetic nephropathy. RASS was based on the concept that slowing the structural changes responsible for renal dysfunction in diabetes2,3 would delay or prevent clinical diabetic nephropathy.
Recently, the Diabetic Retinopathy Candesartan Trials (DIRECT; ClinicalTrials.gov numbers, NCT00252733 [ClinicalTrials.gov] , NCT00252720 [ClinicalTrials.gov] , and NCT00252694 [ClinicalTrials.gov] ) reported that angiotensin-receptor blockade reduced the rate of retinopathy development in normotensive patients with type 1 diabetes and normoalbuminuria who did not have diabetic retinopathy12 but not in patients with mild-to-moderate diabetic retinopathy. Our study was designed to assess the effect of renin–angiotensin system blockade with either an angiotensin-converting–enzyme (ACE) inhibitor or an angiotensin-receptor blocker (AR on both renal and retinal morphologic features in normotensive patients with type 1 diabetes and normoalbuminuria.13
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. 本人已认领该文编译，48小时后若未提交译文，请其他战友自由认领。 Renal and Retinal Effects of Enalapril and Losartan in Type 1 Diabetes
依那普利和氯沙坦对1型糖尿病患者肾脏及视网膜的作用
Diabetic nephropathy, responsible for more than 45% of cases of end-stage renal disease in the United States, may be structurally advanced once albuminuria becomes detectable.
糖尿病肾病在美国是愈45%终末期肾病的病因，当有肾脏病理改变时可检测到白蛋白尿。
Blockers of the renin–angiotensin system are more effective than other antihypertensive agents in slowing nephropathy progression in patients who have proteinuria, diabetes mellitus, and a reduced glomerular filtration rate (GFR) and such blockers can also decrease proteinuria in patients with diabetes.
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作者:admin@医学,生命科学 2010-10-21 17:11
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