What does this research mean for the field?

In patients with diabetic nephropathy, combining an angiotensin II receptor antagonist with an ACE inhibitor attenuates angiotensin II effects more effectively than ACE inhibitor therapy alone. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

January 1, 1999

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

Structured PICO

Does the addition of losartan to ACE inhibitor therapy attenuate AngII effects (measured by plasma renin levels) in patients with diabetic nephropathy?

Population

7 inpatients with diabetic nephropathy on a usual regimen including daily oral moderate to high dose ACE inhibitor therapy.

Intervention

Oral losartan 50 mg (n=3) or 100 mg (n=4) daily added to usual ACE inhibitor therapy for 1 week.

Comparator

Usual regimen of ACE inhibitor therapy alone (within-subject comparison during week 1 baseline and week 3 washout).

Outcome

Plasma renin levelssurrogate

In a small short-term study, adding losartan to ACE inhibitor therapy in diabetic nephropathy significantly increased plasma renin levels, suggesting enhanced attenuation of AngII effects.

Abstract

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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