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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: ASN.2009070737v1 20/12/2641    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Mehdi, U. F. Articles by Toto, R. D. PubMed PubMed Citation Articles by Mehdi, U. F. Articles by Toto, R. D. Related Collections Related Articles

Addition of Angiotensin Receptor Blockade or Mineralocorticoid Antagonism to Maximal Angiotensin-Converting Enzyme Inhibition in Diabetic Nephropathy

Uzma F. Mehdi^*, Beverley Adams-Huet^*,, Philip Raskin^*, Gloria L. Vega and Robert D. Toto^*,

*Department of Internal Medicine,
Center for Human Nutrition, and
Department of Clinical Sciences, The University of Texas Southwestern Medical Center, Dallas, Texas

Correspondence: Dr. Robert D. Toto, 5939 Harry Hines Boulevard, University of Texas Southwestern Medical Center, Dallas, Texas 75930. Phone: 214-645-8268; Fax 214-645-8903; E-mail: robert.toto{at}utsouthwestern.edu

Received for publication July 20, 2009. Accepted for publication September 22, 2009.

Aldosterone promotes glomerular and tubular sclerosis independent of angiotensin II in animal models of diabetic nephropathy. Most human studies testing the renoprotective benefit of adding an angiotensin receptor blocker or a mineralocorticoid receptor antagonist to a regimen based on inhibition of angiotensin-converting enzyme (ACE) used relatively low doses of ACE inhibitors. Furthermore, these studies did not determine whether antiproteinuric effects were independent of BP lowering. We conducted a double-blind, placebo-controlled trial in 81 patients with diabetes, hypertension, and albuminuria (urine albumin-to-creatinine ratio 300 mg/g) who all received lisinopril (80 mg once daily). We randomly assigned the patients to placebo, losartan (100 mg daily), or spironolactone (25 mg daily) for 48 wk. We obtained blood and urine albumin, urea, creatinine, electrolytes, A1c, and ambulatory BP at baseline, 24, and 48 wk. Compared with placebo, the urine albumin-to-creatinine ratio decreased by 34.0% (95% CI, –51.0%, –11.2%, P = 0.007) in the group assigned to spironolactone and by 16.8% (95% CI, –37.3%, +10.5%, P = 0.20) in the group assigned to losartan. Clinic and ambulatory BP, creatinine clearance, sodium and protein intake, and glycemic control did not differ between groups. Serum potassium level was significantly higher with the addition of either spironolactone or losartan. In conclusion, the addition of spironolactone, but not losartan, to a regimen including maximal ACE inhibition affords greater renoprotection in diabetic nephropathy despite a similar effect on BP. These results support the need to conduct a long-term, large-scale, renal failure outcomes trial.

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				M. F. Rubin and R. R. Townsend Aldosterone Blockade in Diabetic Nephropathy: Relative Risks and Potential Promise J. Am. Soc. Nephrol., December 1, 2009; 20(12): 2487 - 2489. [Full Text] [PDF]

Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673