Nephrol Dial Transplant (2002) 17: 1019-1024
© 2002 European Renal Association-European Dialysis and Transplant Association
Dual blockade of the renin–angiotensin system in type 1 patients with diabetic nephropathy
Steno Diabetes Center, Gentofte, Denmark
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 m2. 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.
Keywords: ACE inhibition; albuminuria; Irbesartan angiotensin II receptor blockade; blood pressure; diabetic nephropathy; glomerular filtration rate; renin–angiotensin system; type 1 diabetes
Correspondence and offprint requests to: Peter Jacobsen, Steno Diabetes Center, Niels Steensens Vej 2, DK-2820 Gentofte, Denmark. Email: pkjacobsen{at}dadlnet.dk
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