Journal Article

Early treatment with everolimus exerts nephroprotective effect in rats with adriamycin-induced nephrotic syndrome

Rawi Ramadan, Diana Faour, Hoda Awad, Eleanor Khateeb, Ravit Cohen, Ali Yahia, Rafael Torgovicky, Raanan Cohen, David Lazari, Hiroshi Kawachi and Zaid Abassi

in Nephrology Dialysis Transplantation

Published on behalf of European Renal Association - European Dialysis and Transplant Assoc

Volume 27, issue 6, pages 2231-2241
Published in print June 2012 | ISSN: 0931-0509
Published online October 2011 | e-ISSN: 1460-2385 | DOI: http://dx.doi.org/10.1093/ndt/gfr581
Early treatment with everolimus exerts nephroprotective effect in rats with adriamycin-induced nephrotic syndrome

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Background.

Nephrotic syndrome (NS) is a clinical state characterized by massive proteinuria and excessive fluid retention. The effects of early versus late treatment with low or high doses of oral everolimus, a mammalian target of rapamycin inhibitor, on proteinuria in NS have not been previously described.

Methods.

The effects of early treatment (2 days prior to NS induction) versus late treatment (beginning 2 weeks following the establishment of NS) with a low (20 mg/L) or high (100 mg/L) dose of everolimus for 5–7 weeks on proteinuria and nephrin/podocin abundance were assessed in male adult SD rats with adriamycin-induced NS.

Results.

Adriamycin caused a significant increase in daily and cumulative proteinuria throughout the experimental period. Early, and to a lesser extent late treatment, with a low dose of everolimus, significantly decreased both daily and cumulative proteinuria and improved renal function. The anti-proteinuric effects of low-dose everolimus were associated with restoration of the disruptive glomerular nephrin/podocin abundance. In contrast, administration of a high dose of everolimus resulted in a decrease in proteinuria in NS rats, subsequently to deterioration of renal function.

Conclusions.

Early, and to a lesser extent late treatment, with a low but not a high dose of everolimus is effective in reducing proteinuria in nephrotic rats. The mechanism may be via nephrin/podocin protection.

Keywords: adriamycin; clearance; everolimus; nephrotic syndrome; proteinuria; rat

Journal Article.  5584 words.  Illustrated.

Subjects: Nephrology

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