PLACEBO-CONTROLLED TRIAL OF LISINOPRIL IN NORMOTENSIVE DIABETIC-PATIENTS WITH INCIPIENT NEPHROPATHY

To study the effects of an angiotensin converting enzyme inhibitor, li sinopril, on renal function in incipient diabetic nephropathy, a prosp ective double-blind randomised placebo-controlled single centre study was set up at our outpatient diabetic-renal clinic. There were 27 pati ents with Type I and Type II diabetes with an albumin excretion rate o f between 20 mug/min and 200 mug/min, respectively and no hypertension . Intervention treatment with placebo or low dose lisinopril was for 4 8 weeks. The main outcome changes were in urinary albumin excretion ra te, urinary prostaglandin excretion, and glomerular filtration rate. S econdary outcome measures included changes in BP and heart rate. Of th e 32 patients entered into the study, 27 completed 48 weeks treatment (12 lisinopril, 15 placebo). Mean (+/- SD) urinary albumin excretion r ate fell from 57.6 (25.7) mug/min (n = 15) at visit 1 to 26.8 (26.7) m ug/min (n = 12) at visit 7 after 48 weeks treatment in the lisinopril group but not in the placebo group: 119.2 (I 16.6) mug/min (n = 17) vs . 11 3.7 (77.0) mug/min (n = 15) There was a least squares mean treatm ent difference of -67.6 mug/min (95% confidence interval (CI), -115.0 to -20.2, P < 0.01) in favour of lisinopril compared with placebo. Aft er 48 weeks treatment seven lisinopril treated patients were normoalbu minuric and five were microproteinuric; three placebo treated patients were normoalbuminuric, nine were microalbuminuric and three were macr oproteinuric. Excretion of prostaglandin-F1alpha (PGF1alpha) and throm boxane-B2 (TXB2) fell in the lisinopril treated group. Treatment diffe rences between groups were not significant (-18.9 pg/min, 95% Cl -138. 6 to 100.9, P = 0.74 for PGF1alpha and 105.4 pg/min, 95% Cl -385.2 to 174.4, P = 0.43 for TXB2) in favour of lisinopril (n = 9) compared wit h placebo (n = 8). Glomerular filtration rate fell from 126.9 (46.7) t o 100.8 (27.4) ml/min per 1.73 m2 (n = 15) for lisinopril and from 110 .8 (34.0) to 103.1 (38.3) ml/min per 1.73 m2 (n = 17) for placebo trea ted patients. The decrease was larger in the lisinopril group (15.7 ml /min per 1.73 m2, 95% Cl -41,5 to 10.1, P = 0.22). Heart rate did not alter significantly in either group: 78.5 (13.9)beats/min at visit 1 a nd 80.5 (11.8) beats/min at visit 7 for lisinopril and 80.9 (10.4) bea ts/min and 79.9 (8.4) beats/min for placebo treated. SBP fell in the l isinopril group from 137 (20) mmHg (n = 15) to 125 (19) mmHg (n = 12) but did not after in the placebo group: 136 (26) mmHg (n = 17) and 138 (23) mmHg (n = 15). The treatment of normotensive microproteinuric di abetic patients. with lisinopril for 48 weeks appears to protect again st the development of macroalbuminuria. The reduction in urinary album in excretion rate appears to be independent of reductions in systemic BP or alterations in urinary prostaglandin excretion.