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Dual blockade of the renin-angiotensin system in type 1 patients with diabetic nephropathy

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BACKGROUND: Albuminuria and hypertension are predictors of poor renal and cardiovascular outcome in patients with diabetes. Approximately 30% of type 1 patients with diabetic nephropathy (DN) have albuminuria >1 g/day, and blood pressure >135 and/or >85 mmHg despite antihypertensive therapy with recommended doses of ACE inhibitor (ACEI) and diuretics. We tested the effect of dual blockade of the renin-angiotensin system (RAS) in these patients.

METHODS: We performed a randomised double blind crossover trial with 2 months treatment with Irbesartan 300 mg o.d. and placebo added on top of previous antihypertensive treatment. We included 21 type 1 patients with DN responding insufficiently to ACEI and diuretics, as defined above. At the end of each treatment period, albuminuria, 24-h blood pressure and glomerular filtration rate (GFR) were measured.

RESULTS: Addition of 300 mg Irbesartan to the patients' usual antihypertensive therapy induced a mean reduction in albuminuria of 37% (95% CI 20-49, P<0.001); from 1574 mg/24 h (95% CI 1162-2132) to 996 mg/24 h (95% CI 699-1419), a reduction in 24-h blood pressure of 8 mmHg systolic (95% CI -2 to 18) and 5 mmHg diastolic (95% CI 1-9) (P=0.11 and 0.01, respectively) (from placebo, mean (SE) 146 (4)/80 (2) mmHg). GFR remained unchanged. Serum potassium increased (mean 4.3 to 4.6 mmol/l, P=0.02). Intervention to reduce serum potassium was needed in two patients with GFR <35 ml/min/1.73 m(2). Otherwise the dual blockade with Irbesartan was safe and well tolerated.

CONCLUSIONS: Dual blockade of the RAS may offer additional renal and cardiovascular protection in type 1 patients with DN responding insufficiently to conventional antihypertensive therapy, including recommended doses of ACEI and diuretics.

Original languageEnglish
JournalNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
Volume17
Issue number6
Pages (from-to)1019-24
Number of pages6
ISSN0931-0509
DOIs
Publication statusPublished - Jun 2002

    Research areas

  • Albuminuria/drug therapy, Angiotensin-Converting Enzyme Inhibitors/therapeutic use, Antihypertensive Agents/therapeutic use, Biphenyl Compounds/therapeutic use, Blood Pressure, Cross-Over Studies, Diabetes Mellitus, Type 1/drug therapy, Diabetic Nephropathies/drug therapy, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Irbesartan, Male, Middle Aged, Placebos, Renin-Angiotensin System, Tetrazoles/therapeutic use

ID: 59053989