Thymoglobulin Administered to Donors: Its Protective Effect Against Ischemia Reperfusion Injury Process in Kidney Transplantation

CICORA FEDERICO; LAUSADA NATALIA; GONZALEZ PEDRO; STRINGA PABLO; GUERRIERI DIEGO; VUKON IVANA; CICORA PAOLA; PALTI GUSTAVO; RAIMONDI CLEMENTE

FILADELFIA

Congreso; American Transplantation Congress 2011; 2011

AMERICAN SOCIETY OF TRANSPLANTATION

Introduction: IRI after kidney transplantation is a factor responsible for DGF. It can increase the risk of acute rejection and it has an impact on allograft survival. Renal isogenic transplantation is a widespread model used to study non-immunological damage. Our aim was to determine whether donor treatment with an anti-rat analog of Thymoglobulin (produced in rabbits using similar processes to commercial Thymoglobulin) could attenuate the IRI process. Materials and methods: G1 (n=6): Sham operated. G2 (n=6): Control Group: Donor left kidneys were removed and preserved in lactated Ringer´s solution for 3 h at 4 C. Following preservation, kidneys were transplanted into recipient after they underwent bilateral nephrectomy. G3 (n=6): same surgical procedure as in G2; however, a rat analog of Thymoglobulin (10 mg/kg) was administered to donors 12 h before removal of the kidney. None of the groups received immunosuppressive treatment after transplantation. Plasma urea and creatinine levels were determined at baseline and 24 h post transplant. Histological samples were analyzed for tubular injury by a score according to five grades of cortex and outer medula involvement. Finally, apoptosis was assessed by TUNEL assay. Results: G1 hasn´t shown any difference between pre and post procedure creatinine and urea values. Urea: G2: 211± 8 mg/dl vs G3: 110 ± 15 mg/dl (p<0.001). Creatinine: G2: 4.6 ± 0.24 mg/dl vs G3: 2.6 ± 0.22 mg/dl (p<0.001). Histological Score G2: 2.3 vs G3: 1.6 (p<0.05). TUNEL: G2: 80 ± 13 vs G3: 9± 3 apoptotic cells (p<0.001). The administration of Thymoglobulin to donors produced a reduction of TNFá, IL6, IL21 and an increase of BCL2 and HO1. No differences were found in the expression of IL17, C3 and Bax. Conclusions: A rat analog of Thymoglobulin administration to donors attenuates IRI process as evidenced by renal function improvement and a significant reduction in apoptosis and necrosis of tubular epithelial cells. Both apoptosis pathways would be affected by TNFá reduction and BCL2 upregulation. Moreover, there appears a significant reduction of proinflammatory cytokines by the administration of anti-rat Thymoglobulin to donor.