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      Combination ACE Inhibitor and Angiotensin II Receptor Antagonist Therapy in Diabetic Nephropathy

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          The benefit of angiotensin-converting enzyme (ACE) inhibitor (i) therapy in diabetic glomerulosclerosis is thought to be largely the result of attenuation of angiotensin II (AngII) effects on blood pressure, glomerular hemodynamics and hypertrophy, and tissue fibrosis. The present study was undertaken to determine whether the addition of AngII receptor antagonist therapy to ACEi therapy in diabetic nephropathy results in attenuation of AngII effects beyond that achieved by ACEi therapy alone. Seven patients were studied as inpatients on the General Clinical Research Center each for 3 consecutive weeks as follows: week 1, the patients’ usual regimen which included daily oral moderate to high dose ACEi therapy; week 2, the patients’ usual regimen plus oral losartan (an antagonist (a) of the angiotensin type 1 receptor, AT1) 50 mg (n = 3) or 100 mg (n = 4) daily; week 3, return to the patients’ usual regimen. Diet, physical activity, and blood glucose were held as constant as possible during the three weeks of daily testing. We found that plasma renin levels increased significantly during combination therapy and then returned to baseline values with discontinuation of AT1a therapy: mean baseline renin values (week 1) 3.0 ng/ml/min ± 1.1 SE, mean renin values during combination therapy (week 2) 7.0 ng/ml/min ± 3.2 (p = 0.0078 by Wilcoxon rank sum test), mean renin values after discontinuation of AT1a 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 creatinine, serum potassium, and plasma aldosterone were not changed significantly by combination therapy. We conclude that in patients with diabetic nephropathy addition of AT1a therapy to ACEi therapy attenuates AngII effects better than ACEi therapy alone. We suggest that combination therapy for the management of diabetic glomerulosclerosis merits further investigation.

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          Angiotensin receptors and their antagonists.

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            The beneficial effect of angiotensin-converting enzyme inhibition with captopril on diabetic nephropathy in normotensive IDDM patients with microalbuminuria


              Author and article information

              Am J Nephrol
              American Journal of Nephrology
              S. Karger AG
              February 1999
              22 March 1999
              : 19
              : 1
              : 1-6
              Department of Internal Medicine, Ohio State University, Columbus, Ohio, USA
              13417 Am J Nephrol 1999;19:1–6
              © 1999 S. Karger AG, Basel

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              Page count
              Figures: 1, Tables: 4, References: 31, Pages: 6
              Self URI (application/pdf): https://www.karger.com/Article/Pdf/13417
              Clinical Study


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