Vol 4, No 3 (2003): Practical Diabetology
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Published online: 2003-05-22

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Long-term renoprotective effects of losartan in diabetic nephropathy. Interaction with ACE insertion/deletion genotype?

Steen Andersen, Lise Tarnow, Francois Cambien, Peter Rossing, Tina R. Juhl, Jaap Deinum, Hans-Henrik Parving
Diabetologia Praktyczna 2003;4(3):211-218.

Abstract

INTRODUCTION. 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.
MATERIAL AND METHODS. A total of 54 hypertensive type 1 diabetic patients with diabetic nephropathy homozygous for the insertion (n = 26) or the deletion (n = 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 vs. DD: mean (SD), 86 (22) vs. 88 (24) ml x min–1 × 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) mm Hg, respectively. GFR decreased similarly in both genotype groups, versus DD, respectively (P = 0.4): geometric mean (95% CI), 2.9 (2.0–4.2) vs. 3.4 (2.3–5.1) ml × min–1 x 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 < 0.01 vs. baseline). Mean systolic and diastolic blood pressures were 139/74 mm Hg (14/8) in both genotype groups during the study (P < 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.

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