Irbesartan reduces creatinine clearance in type 1 diabetic children with renal hyperfunction: a randomized, double-blind, placebo-controlled trial

Abstract

Previous studies in type 2 diabetes have demonstrated the renoprotective effect of AT(1)-receptor antagonist drugs, but data on type 1 diabetic (T1DM) children are scarce. The aim of this study was to evaluate the effectiveness of the AT(1)-receptor antagonist irbesartan in reducing creatinine clearance rate (CCR) in non-hypertensive T1DM children with renal hyperfunction. In this randomized, double-blind, placebo-controlled trial we enrolled 20 T1DM children aged 6-16 years and randomly allocated them to receive either irbesartan (1 mg/kg body weight) or placebo daily for 12 weeks. Children were eligible to participate if they had renal hyperfunction, defined as a CCR >20 ml/min/1.73 m(2) body surface area. In addition, the participants could not have high blood pressure or renal failure and they could not be receiving diuretics or angiotensin-converting enzyme inhibitors. The primary endpoint of the trial was the change in CCR. There were no significant differences in age, duration of diabetes or body mass index between the two groups. No subject dropped out, withdrew consent or had side effects or adverse events attributable to irbesartan or the placebo. In the irbesartan group, CCR decreased from 155.0+/-6.6 to 86.2+/-7.4 ml/min (P<0.0001); CCR did not change significantly in the control group (154.1+/-13.1 to 172.0+/-15.5 ml/min; P = 0.86). Blood pressures at baseline and throughout the study were similar in both groups. Irbesartan significantly reduces CCR in non-hypertensive, non-controlled T1DM children; the clinical significance of this finding, however, remains to be established.