Sirolimus in kidney transplant donors and clinical and histologic improvement in recipients: rat model.

BACKGROUND

Ischemia-reperfusion (I/R) injury is one of the risk factors for delayed graft function, acute rejection episodes, and impaired long-term allograft survival after kidney transplantation. This antigen-independent inflammatory process produces tissue damage. Isogeneic transplantation in a rat model is a useful method for study of nonimmunologic risk factors for kidney damage.

OBJECTIVE

To study the effect of sirolimus on I/R injury using only 1 dose of the drug in the donor.

MATERIALS AND

METHODS

Eighteen rats were allocated to 3 groups of 6 rats each: sham group, control group, and rapamycin group.

RESULTS

Improved renal function and systemic inflammatory response were observed in the rapamycin group compared with the control group (Deltaurea, Deltacreatinine, and DeltaC3, all P < .01). The number of apoptotic nuclei in the renal medulla in the control group was higher than in the rapamycin group (P < .01). Tubular damage was less severe in the rapamycin group compared with the control group (P < .01). Complement 3 and tumor necrosis factor-alpha expression in the kidney samples were significantly decreased when rapamycin was given to the donor rats (P > .01). Bcl-2 protein was upregulated in the rapamycin group compared with the control group (P < .01).

CONCLUSION

Administration of rapamycin in donors attenuates the I/R injury process after kidney transplantation in a rat model.