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.


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).


CONCLUSIONS
Administration of rapamycin in donors attenuates the I/R injury process after kidney transplantation in a rat model.
Cicora
F
F
Universidad Nacional de la Plata, La Plata, Argentina. fcicora5@gmail.com
Lausada
N
N
Vasquez
D N
DN
Cicora
P
P
Zalazar
G
G
Gonzalez
P
P
Palti
G
G
Raimondi
C
C
D000818:Animals; D003176:Complement C3 / Q000235:genetics; D003404:Creatinine / Q000097:blood; D005786:Gene Expression Regulation / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007677:Kidney Function Tests; D007679:Kidney Medulla / Q000187:drug effects; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D020123:Sirolimus / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014508:Urea / Q000097:blood / Q000378:metabolism
D003176:Complement C3; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D014508:Urea; D003404:Creatinine; D020123:Sirolimus