Long-Term Renoprotective Effects of Losartan in Diabetic Nephropathy
Interaction with ACE insertion/deletion genotype?
- Steen Andersen, MD1,
- Lise Tarnow, MD, DMSC1,
- Francois Cambien, MD2,
- Peter Rossing, MD, DMSC1,
- Tina R. Juhl1,
- Jaap Deinum, MD3 and
- Hans-Henrik Parving, MD, DMSC14
- 1Steno Diabetes Center, Copenhagen, Denmark
- 2INSERM U525, Paris, France
- 3Department of Internal Medicine I, University Hospital Dijkzigt, Rotterdam, the Netherlands
- 4Faculty of Health Science, Aarhus University, Aarhus, Denmark
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 = 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 versus DD: mean (SD), 86 (22) vs. 88 (24) ml · 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) mmHg, 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 · 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 mmHg (14/8) in both genotype groups during the study (P < 0.01 vs. baseline).
CONCLUSIONS—In contrast to previous observational studies with ACE inhibitors, long-term 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.
- ACE/ID, insertion/deletion polymorphism of the ACE gene
- AT1, angiotensin II subtype-1
- GFR, glomerular filtration rate
- MABP, mean arterial blood pressure
Address correspondence and reprint requests to Steen Andersen, Steno Diabetes Center, Niels Steensensvej 2, 2820 Gentofte. E-mail:.
Received for publication 20 September 2002 and accepted in revised form 22 November 2002.
S.A. receives funding from Merck & Co. for research studies on new treatments in diabetic nephropathy. H-H.P. holds stock in Novo Nordisk, which makes products related to the treatment of diabetes; has received honoraria for speaking engagements from Merck & Co.; and receives funding from Merck & Co., Astra Corporation, and Sanofi Corporation for research studies on new treatments in diabetic retinopathy.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances
See accompanying editorial, p. 1631.
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