title: Sirolimus prevents short-term renal changes induced by ischemia-reperfusion injury in rats.
abstract: 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.
authors.affiliation: Units of Nephrology, Dialysis and Transplantation, Policlinico San Matteo, University of Pavia, Italy. espositociro56@live.it
authors.forename: C
authors.initials: C
authors.lastname: Esposito
authors.forename: F
authors.initials: F
authors.lastname: Grosjean
authors.forename: M
authors.initials: M
authors.lastname: Torreggiani
authors.forename: V
authors.initials: V
authors.lastname: Esposito
authors.forename: F
authors.initials: F
authors.lastname: Mangione
authors.forename: L
authors.initials: L
authors.lastname: Villa
authors.forename: G
authors.initials: G
authors.lastname: Sileno
authors.forename: R
authors.initials: R
authors.lastname: Rosso
authors.forename: N
authors.initials: N
authors.lastname: Serpieri
authors.forename: M
authors.initials: M
authors.lastname: Molinaro
authors.forename: G
authors.initials: G
authors.lastname: Fasoli
authors.forename: A
authors.initials: A
authors.lastname: Dal Canton
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000473:pathology / Q000517:prevention & control*; D007677:Kidney Function Tests; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D020123:Sirolimus / Q000627:therapeutic use*; D016559:Tacrolimus / Q000627:therapeutic use*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D020123:Sirolimus; D016559:Tacrolimus