OBJECTIVE -Several observational follow-up studies have found that the D allele of the insertion (I)/deletion (D) polymorphism of the ACE gene (ACE/ID) is associated with an increased risk of renal function loss, even during ACE inhibition. Therefore, we investigated the long-term effect of the angiotensin II subtype-1 (AT1) receptor antagonist losartan (100 mg o.d.) on kidney function in II and DD type 1 diabetic patients with diabetic nephropathy.
RESEARCH DESIGN AND METHODS-A total of 54 hypertensive type 1 diabetic patients with diabetic nephropathy homozygous for the insertion (n ϭ 26) or the deletion (n ϭ 28) allele were included in the study. After a 4-week washout, the patients received losartan (tablet, 100 mg o.d.) and were followed prospectively with a mean follow-up period of 36 months. Patients and investigators were blinded to ACE genotypes. At baseline, after 2 and 4 months and every 6 months thereafter, glomerular filtration rate (GFR), albuminuria, and 24-h blood pressure were determined.RESULTS -At baseline, GFR, albuminuria, and blood pressure were similar in the two genotype groups, II versus DD: mean (SD), 86 (22) vs. 88 (24) ml ⅐ min -1 ⅐ 1.73 m -2 ; median (interquartile range), 1,134 (598 -2,023) vs. 1,451 (893-1,766) mg/24 h; and mean (SD), 156/82 (17/9) vs. 153/80 (17/11) mmHg, respectively. GFR decreased similarly in both genotype groups, versus DD, respectively (P ϭ 0.4): geometric mean (95% CI), 2.9 (2.0 -4.2) vs. 3.4 (2.3-5.1) ml ⅐ min -1 ⅐ year -1 . Albuminuria and arterial blood pressure were significantly reduced during the study; no differences were noted between groups. During follow-up, albuminuria was decreased by 75% (95% CI 59 -85) and 73% (56 -83) in the II and DD groups, respectively (P Ͻ 0.01 vs. baseline). Mean systolic and diastolic blood pressures were 139/74 mmHg (14/8) in both genotype groups during the study (P Ͻ 0.01 vs. baseline).CONCLUSIONS -In contrast to previous observational studies with ACE inhibitors, longterm treatment with losartan has similar beneficial renoprotective effects on progression of diabetic nephropathy in hypertensive type 1 diabetic patients with ACE II and DD genotypes.