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Original Paper

Proinflammatory Effects in Experimental Mesangial Proliferative Glomerulonephritis of the Immunosuppressive Agent SDZ RAD, a Rapamycin Derivative

Daniel C. · Ziswiler R. · Frey B. · Pfister M. · Marti H.P.

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Division of Nephrology and Hypertension, Department of Medicine, Inselspital, Bern, Switzerland

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Exp Nephrol 2000;8:52–62

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: January 14, 2000
Issue release date: January – February

Number of Print Pages: 11
Number of Figures: 4
Number of Tables: 3


eISSN: 1660-2129 (Online)

For additional information: https://www.karger.com/NEE

Abstract

Background/Aim: The new immunosuppressant SDZ RAD, a rapamycin derivative, inhibits growth factor driven cell proliferation. SDZ RAD designed for transplantation may also be a candidate agent to treat inflammatory kidney diseases. Therefore, we investigated the effects of SDZ RAD in two different animal models of glomerulonephritis, in anti- Thy1.1 nephritis and in acute puromycin aminonucleoside (PAN) nephrosis. Methods: Eighty-seven male Wistar rats were investigated. Anti-Thy1.1 nephritis: healthy rats (n = 9), SDZ RAD-treated healthy rats (n = 6), nephritic rats (n = 9), SDZ RAD placebo treated nephritic rats (n = 6), SDZ RAD-pretreated nephritic rats (n = 9), and early (n = 6) as well as delayed (n = 6) SDZ RAD-posttreated nephritic rats. PAN nephrosis: healthy rats (n = 6), SDZ RAD-treated healthy rats (n = 6), nephritic rats (n = 12), and SDZ RAD-pretreated nephritic rats (n = 12). In a separate study, 12 male Sprague-Dawley rats were analyzed in anti-Thy1.1 nephritis: healthy rats (n = 3), nephritic rats (n = 3) and pretreated nephritic rats (n = 6). SDZ RAD and SDZ RAD placebo were given at single doses of 2.5 mg/kg body weight per day by gavage. The experiments lasted until days +2 and +9 after induction of anti-Thy1.1 nephritis and until day +13 in the case of PAN nephrosis. Results: In anti-Thy1.1 nephritis, SDZ RAD demonstrated marked proinflammatory effects in a time-dependent manner, as reflected by severe focal damage to glomerular histology including inhibition of mesangial cell proliferation, reduction of creatinine clearance, and increase in plasma creatinine levels as well as proteinuria. Almost identical results were obtained in both rat strains. In contrary, SDZ RAD ameliorated significantly the development of PAN nephrosis. Animals pretreated by this agent showed a significant reduction of proteinuria and of glomerular invasion of monocytes/macrophages. Conclusion: Some caution is warranted for the use of SDZ RAD in inflammatory glomerular diseases, since it accentuated glomerular damage induced by anti-Thy1.1 antibodies.

© 2000 S. Karger AG, Basel


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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Published online: January 14, 2000
Issue release date: January – February

Number of Print Pages: 11
Number of Figures: 4
Number of Tables: 3


eISSN: 1660-2129 (Online)

For additional information: https://www.karger.com/NEE


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