Sirolimus prevents short-term renal changes induced by ischemia-reperfusion injury in rats

C. Esposito, F. Grosjean, M. Torreggiani, V. Esposito, F. Mangione, L. Villa, G. Sileno, R. Rosso, N. Serpieri, M. Molinaro, G. Fasoli, A. Dal Canton

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Background: Ischemia-reperfusion (I/R) is present at various degrees in kidney transplants. I/R plays a major role in early function and long-term survival of renal allograft. The purpose of our study was to determine if immunosuppressants modulate I/R in a model that separates I/R from all immune responses. Methods: Sprague-Dawley rats with monolateral renal I/R received daily cyclosporine (A), tacrolimus (B), sirolimus (C) or saline (D). Sham-operated rats received saline (E). After 30 days, glomerular filtration rate for each kidney was measured by inulin clearance. Kidney injury was examined, and TGF-β, fibronectin and metalloproteases were evaluated by real-time PCR, Western blot and zymography. Results: Sirolimus, but not cyclosporine and tacrolimus, prevented a glomerular filtration rate decrease in I/R kidneys (403 ± 303 vs. 1,006 ± 484 μl/min, p <0.05; 126 ± 170 vs. 567 ± 374 μl/min, p <0.05; 633 ± 293 vs. 786 ± 255; A, B and C group, respectively, I/R vs. contralateral kidneys). Sirolimus reduced ED-1+ cell infiltrate, interstitial fibrosis and intimal thickening of small vessels observed in I/R kidneys of controls and calcineurin inhibitor-treated rats. Tacrolimus and cyclosporine increased fibronectin and TGF-β expression and matrix deposition. Only sirolimus increased metalloprotease activity. Conclusions: Sirolimus but not calcineurin inhibitors prevented I/R-induced kidney injury.

Original languageEnglish
Pages (from-to)239-249
Number of pages11
JournalAmerican Journal of Nephrology
Issue number3
Publication statusPublished - Mar 2011


  • Immunosuppressive drugs
  • Ischemia-reperfusion injury
  • Metalloprotease activity

ASJC Scopus subject areas

  • Nephrology

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