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1 Ambulatory Nephrology Unit, Rambam:Human health Care Campus, Haifa, Israel; , Israel
2 Vascular and Molecular Medicine, Beth Israel Deaconess Medical Center Harvard Medical School, Boston, Massachusetts, United States
3 Medicine, Technion, Israel
4 Department of Cell Biology, Institute of Nephrology, Faculty of Medicine, Niigata University, Niigata, Niigata, Japan
5 Vascular Surgery & Transplantation, Rambam: Human Health Care Campus, Haifa, Israel
6 Physiology and Biophysics, Technion, Israel
7 medicine, Semmelweis University, Hungary
8 Physiology and Biophysics, Faculty of Medicine, Technion, Haifa, Israel
* To whom correspondence should be addressed. E-mail: f_nakhoul{at}rambam.health.gov.il.
Nephrotic syndrome 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 antiproteinuric effects of eplerenone alone or combined with enalapril on nephrin/podocin abundance in rats with NS have not been studied yet. Therefore, the present study was designed to examine the early (beginning 2 days before NS induction) and late (beginning 2 weeks 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 (Upr.V) (from 26.96+/-3.43 to 958.57+/-56.7 mg/day, P<0.001) and cumulative proteinuria (from 900.33+/-135.5 mg to 22490.62+/-931.26 mg,(P<0.001) during 6 weeks. Early treatment with enalapril significantly decreased Upr.V from 958.6+/-56.7 to 600.31+/-65.13 mg/day, p<0.001) and cumulative proteinuria to 12842.37+/-1798.17 mg/6weeks,(P<0.001). Similarly early treatment with eplerenone produced profound anti proteinuric effect: Upr.V decreased from 958.57+/-56.7 mg/day to 593.38+/-21.83 mg/day, p<0.001; and cumulative proteinuria to 16601.84+/-1334.31 mg/6weeks; P<0.001. Additive effect was obtained when enalapril and eplerenone were combined: Upr.V decreased from 958.57+/-56.69 to 424.17+/-38.54 mg/day;P<0.001; and cumulative protein excretion declined to 10252.88+/-1011.3 mg/6weeks;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 Upr.V 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 anti-proteinuric effects were obtained when enalapril and eplerenone were combined.
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