Mechanisms of everolimus‐induced glomerulosclerosis after glomerular injury in the rat

Daniel C, Renders L, Amann KU, Schulze-Lohoff E, Hauser IA, Hugo C (2005)

Publication Language: English

Publication Type: Journal article

Publication year: 2005

Journal

American Journal of Transplantation Wiley

Book Volume: 5

Pages Range: 2849-2861

Journal Issue: 12

DOI: 10.1111/j.1600-6143.2005.01120.x

Abstract

Despite the lack of nephrotoxicity, adverse effects of the new antiproliferative immunosuppressant everolimus have been reported. By varying time point and dose of everolimus treatment as well as the degree of glomerular injury, the specific conditions and potential mechanisms leading to adverse actions in the anti-Thy1 model have been determined. Only the combination of early and high-dose everolimus treatment (1-3 mg/kg bw) with a severe glomerular lesion ('full-dose' anti-Thy1 model) caused adverse effects with a high mortality rate, progressive apoptosis, crescent formation and glomerulosclerosis. In contrast, either later start or low-dose (0.3 mg/kg bw) therapy or treatment of a less severe lesion ('reduced dose' anti-Thy1 model) appeared to be relatively safe for the glomerular architecture. The adverse effects of everolimus were linked to its marked inhibition of endothelial cell, but not necessarily mesangial cell proliferation. In addition, everolimus markedly inhibited the angiogenic cytokine vascular endothelial growth factor in nephritic glomeruli in vivo. These experimental results suggest special caution regarding the use of everolimus in all situations of severe glomerular cell injury requiring extensive capillary repair, where at least adaption to a low dose needs to be considered. Copyright © Blackwell Munksgaard 2005.

Authors with CRIS profile

Christoph Daniel Department of Nephropathology Kerstin Ute Amann Professur für Nephropathologie

Involved external institutions

Goethe-Universität Frankfurt am Main DE Germany (DE) Krankenhaus Köln-Merheim - Klinikum der Universität Witten/Herdecke DE Germany (DE)

How to cite

APA:

Daniel, C., Renders, L., Amann, K.U., Schulze-Lohoff, E., Hauser, I.A., & Hugo, C. (2005). Mechanisms of everolimus‐induced glomerulosclerosis after glomerular injury in the rat. American Journal of Transplantation, 5(12), 2849-2861. https://doi.org/10.1111/j.1600-6143.2005.01120.x

MLA:

Daniel, Christoph, et al. "Mechanisms of everolimus‐induced glomerulosclerosis after glomerular injury in the rat." American Journal of Transplantation 5.12 (2005): 2849-2861.

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