Preconditioning Donor with a Combination of Tacrolimus and Rapamacyn to Decrease Ischemia Reperfusion Injury in a Rat Syngenic Kidney Transplantation Model*

CICORA FEDERICO; ROBERTI JAVIER; VAZQUEZ DANIELA; GUERRIERI DIEGO; LAUSADA NATALIA; CICORA PAOLA; PALTI GUSTAVO; CHULUYAN EDUARDO; GONZALEZ PEDRO; STRINGA PABLO; RAIMONDI CLEMENTE

CLINICAL AND EXPERIMENTAL IMMUNOLOGY

WILEY-BLACKWELL PUBLISHING, INC

Año: 2012 vol. 167 p. 169 - 177

0009-9104

Reperfusion injury remains one of the major problems in transplantation. Repair from ischemic acute renal failure (ARF) involves stimulation of tubular epithelial cell proliferation. The aim of this exploratory study was to evaluate the effect ofpreconditioning donors with Rapamycin and Tacrolimus to prevent I/R injury. Twelve hours before nephrectomy, donor Wistar rats received immunosuppressive drugs. Animals were divided in four groups. Group 1 Control: no treatment, Group 2: Rapamycin (2 mg/Kg), Group 3 FK506 (0, 3 mg/kg) and Group 4: FK506 (0,3 mg/kg) plus Rapamycin (2 mg/Kg). Left kidney was removed and after three hours of cold ischemia, graft was transplanted. Twenty four hours after transplant kidney was recovered for histological analysis and cytokine expression. Preconditioning treatment with Rapamycin or Tacrolimus significantly reduced blood urea nitrogen and creatinine compared with Control (BUN: p< 0.001 vs. Control and Creatinine: p<0.001 vs. Control). A further decrease was observed when Rapamycin was combined with Tacrolimus. Acute tubular necrosis was significantly decreased in donor treated with immunosuppressants compared with Control group (P < 0.001 vs. Control). Moreover, the number of apoptotic nuclei in Control group were higher compared with treated groups (p<0.001 vs. Control). Surprisingly, only Rapamycin preconditioning treatment increased anti-apoptotic Bcl2 levels (p<0.001). Finally, inflammatory cytokines, such as TNF-á and IL-6, showed lower levels in the graft of those animals pre-treated with Rapamycin or Tacrolimus. This exploratory study demonstrates that preconditioning donors with Rapamycin or Tacrolimus appears to improve clinical outcomes and reduce necrosis and apoptosis in kidney I/R injury.