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This Article Full Text Full Text (PDF) All Versions of this Article: 294/3/F628    most recent 00524.2007v1 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 Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nakhoul, F. Articles by Abassi, Z. Search for Related Content PubMed PubMed Citation Articles by Nakhoul, F. Articles by Abassi, Z.

Eplerenone potentiates the antiproteinuric effects of enalapril in experimental nephrotic syndrome

¹Ambulatory Nephrology Unit and ⁴Department of Vascular Surgery, Rambam-Health Care Campus, and ²Department of Physiology and Biophysics, Rappaport Family Institute for Research in the Medical Sciences, Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel; ³Department of Cell Biology, Institute of Nephrology, Niigata, University Graduate School of Medical and Dental Sciences, Niigata, Japan; ⁵Faculty of Medicine, Semmelweis University, Budapest, Hungary; and ⁶Division of Molecular and Vascular Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts

Submitted 7 November 2007 ; accepted in final form 13 December 2007

Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria and edema. It is believed that nephrin and podocin are involved in the development of proteinuria. The proteinuria and effects of eplerenone alone or combined with enalapril on nephrin/podocin abundance in rats with NS have not yet been studied. Therefore, the present study was designed to examine the early (beginning 2 days before NS induction) and late (beginning 2 wk after NS induction) effects of eplerenone and enalapril, alone or combined, on proteinuria and nephrin/podocin abundance in rats with adriamycin-induced NS. Adriamycin caused a significant increase in daily protein excretion (U_prV; from 26.96 ± 3.43 to 958.57 ± 56.7 mg/day, P < 0.001) and cumulative proteinuria [from 900.33 ± 135.5 to 22,490.62 ± 931.26 mg (P < 0.001)] during 6 wk. Early treatment with enalapril significantly decreased U_prV from 958.6 ± 56.7 to 600.31 ± 65.13 mg/day (P < 0.001) and cumulative proteinuria to 12,842.37 ± 1,798.17 mg/6 wk (P < 0.001). Similarly, early treatment with eplerenone produced a profound antiproteinuric effect: U_prV decreased from 958.57 ± 56.7 to 593.38 ± 21.83 mg/day, P < 0.001, and cumulative proteinuria to 16,601.84 ± 1,334.31 mg/6 wk; P < 0.001. An additive effect was obtained when enalapril and eplerenone were combined: U_prV decreased from 958.57 ± 56.69 to 424.17 ± 38.54 mg/day, P < 0.001, and cumulative protein excretion declined to 10,252.88 ± 1,011.3 mg/6 wk, P < 0.001. These antiproteinuric effects were associated with substantial preservation of glomerular nephrin and podocin. In contrast, late treatment with either enalapril or eplerenone alone or combined mildly decreased U_prV and cumulative proteinuria. Thus pretreatment with eplerenone or enalapril is effective in reducing daily and cumulative protein excretion and preservation of nephrin/podocin. More profound antiproteinuric effects were obtained when enalapril and eplerenone were combined.

adriamycin; proteinuria; nephrin; podocin

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