Long-Term Effect of Lisinopril and Atenolol on Kidney Function in Hypertensive NIDDM Subjects With Diabetic Nephropathy

Abstract

The aim of our study was to evaluate whether inhibition of ACE (lisinopril 10–20 mg/day) can reduce the rate of decline in kidney function more than reducing blood pressure with conventional antihypertensive treatment (atenolol 50–100 mg/day), usually in combination with a diuretic. We performed a prospective, randomized, parallel study for 42 months, double blind for the first 12 months and single blind thereafter. Forty-three (21 lisinopril and 22 atenolol) hypertensive NIDDM patients with diabetic nephropathy were enrolled. Data from 36 patients (17 lisinopril and 19 atenolol, 60 ± 7 years of age, 27 men) who completed at least 12 months of the study period are presented. At baseline, the two groups were comparable: glomerular filtration rate (⁵¹Cr-EDTA plasma clearance) was 75 ± 6 and 74 ± 8 ml · min⁻¹ · 1.73 m⁻², mean 24-h ambulatory blood pressure (A&D TM2420) was 110 ± 3 and 114 ± 2 mmHg, and 24-h urinary albumin excretion rate was 961 (range 331–5,727) and 1,578 (476–5,806) mg/24 h in the lisinopril and atenolol groups, respectively. The mean follow-up time was similar, 37 and 35 months in the lisinopril and atenolol groups, respectively. Mean ambulatory blood pressure was equally reduced in the two groups, 12 ± 2 and 10 ± 2 mmHg in the lisinopril and atenolol groups, respectively. Glomerular filtration rate declined in a biphasic manner with a faster initial (0 to 6 months) change of 1.25 ± 0.49 and 0.81 ± 0.29 ml · min⁻¹ · month⁻¹ followed by a slower sustained decline (6 to 42 months) of 0.59 ± 0.10 and 0.54 ± 0.13 ml · min⁻¹ · month⁻¹ in the lisinopril and atenolol groups, respectively. No significant differences were observed in either initial or sustained decline in glomerular filtration rate between the two groups. Urinary albumin excretion was reduced (% reduction of baseline) more in the lisinopril than in the atenolol group, at 55 (95% CI 29–72) and 15% (−13 to 34), respectively (P = 0.01). In conclusion, the relentless decline in kidney function characteristically found in hypertensive NIDDM patients with diabetic nephropathy can be reduced equally effectively by two antihypertensive treatments, the β-blocker atenolol and the ACE inhibitor lisinopril.