Combination ACE inhibitor and angiotensin II receptor antagonist therapy in diabetic nephropathy

The benefit of angiotensin-converting enzyme (ACE) inhibitor (i) therapy in diabetic glomerulosclerosis is thought to be largely the result of attenua tion of angiotensin II (AngII) effects on blood pressure, glomerular hemody namics and hypertrophy, and tissue fibrosis. The present study was undertak en to determine whether the addition of AngII receptor antagonist therapy t o ACEi therapy in diabetic nephropathy results in attenuation of AngII effe cts beyond that achieved by ACEI therapy alone. Seven patients were studied as inpatients on the General Clinical Research Center each for 3 consecuti ve weeks as follows: week i, the patients' usual regimen which included dai ly oral moderate to high dose ACEI therapy; week 2, the patients' usual reg imen plus oral losartan (an antagonist (a) of the angiotensin type 1 recept or, AT1) 50 mg (n = 3) or 100 mg (n = 4) daily; week 3, return to the patie nts' usual regimen. Diet, physical activity, and blood glucose were held as constant as possible during the three weeks of daily testing. We found tha t plasma renin levels increased significantly during combination therapy an d then returned to baseline values with discontinuation of AT1 a therapy: m ean baseline renin values (week 1) 3.0 ng/ml/min +/- 1.1 SE, mean renin val ues during combination therapy (week 2) 7.0 ng/ml/min +/- 3.2 (p = 0.0078 b y Wilcoxon rank sum test), mean renin values after discontinuation of ATla therapy (week 3) 3.9 ng/ml/min +/- 2.0 (NS compared to baseline values). In addition, 2 patients developed transient hypotension when losartan therapy was initiated. During this short-term study, 24-hour proteinuria, serum cr eatinine, serum potassium, and plasma aldosterone were not changed signific antly by combination therapy. We conclude that in patients with dia betic n ephropathy addition of AT1 a therapy to ACEi therapy attenuates AngII effec ts better than ACEi therapy alone. We suggest that combination therapy for the management of diabetic glomerulosclerosis merits further investigation.