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

Lee A. Hebert, Michael E. Falkenhain, Norris Stanley Nahman, Fernando G. Cosio, Thomas M. O'Dorisio

Research output: Contribution to journalArticle

113 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1-6
Number of pages6
JournalAmerican Journal of Nephrology
Volume19
Issue number1
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

Fingerprint

Angiotensin Receptor Antagonists
Diabetic Nephropathies
Angiotensin-Converting Enzyme Inhibitors
Therapeutics
Renin
Angiotensin II
Losartan
Nonparametric Statistics
Angiotensin Type 1 Receptor
Aldosterone
Serum
Proteinuria
Hypotension
Hypertrophy
Blood Glucose
Inpatients

Keywords

  • Angiotensin blockade
  • Angiotensin inhibition
  • Diabetic nephropathy

ASJC Scopus subject areas

  • Nephrology

Cite this

Combination ACE inhibitor and angiotensin II receptor antagonist therapy in diabetic nephropathy. / Hebert, Lee A.; Falkenhain, Michael E.; Nahman, Norris Stanley; Cosio, Fernando G.; O'Dorisio, Thomas M.

In: American Journal of Nephrology, Vol. 19, No. 1, 01.01.1999, p. 1-6.

Research output: Contribution to journalArticle

Hebert, Lee A. ; Falkenhain, Michael E. ; Nahman, Norris Stanley ; Cosio, Fernando G. ; O'Dorisio, Thomas M. / Combination ACE inhibitor and angiotensin II receptor antagonist therapy in diabetic nephropathy. In: American Journal of Nephrology. 1999 ; Vol. 19, No. 1. pp. 1-6.
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AB - 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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