Article ID Journal Published Year Pages File Type
3392140 Transplant Immunology 2012 7 Pages PDF
Abstract

A major concern in transplantation is the preservation of organ function. Ischemia time and microcirculatory disturbance of the organ cannot be avoided and may result in ischemia reperfusion injury (IRI), increasing the risk of delayed graft function (DGF) and acute and chronic rejection. Anti-thymocyte immunoglobulin (rATG) is a polyclonal antibody preparation with multiple effects when administered to recipients. Our objective has been to evaluate whether the administration of rATG to kidney donors instead of recipients, in an experimental model of syngeneic rat transplantation, ameliorates IRI and facilitates immediate graft function recovery. Urea and creatinine levels and necrosis severity scores were significantly lower in kidneys from donors that had received rATG (urea: control: 211 ± 8 mg/dl vs. treatment: 110 ± 15 mg/dl, p < 0.001; creatinine: control: 4.6 ± 0.24 mg/dl vs. treatment: 2.6 ± 0.22 mg/dl, p < 0.001; necrosis severity scores: control: 2.3 vs. treatment: 1.6, p < 0.05). TUNEL staining showed 80 ± 13 positive cells in control group and 9 ± 3 (p < 0.001) in treatment group. In situ expression of proinflammatory cytokines TNF-α, IL-6, IL-21 and TGF-β1 was reduced in rATG group (p < 0.01); the same was observed for KIM-1 and caspase 8 (p < 0.001). Cytoprotective genes Bcl2 and HO-1 were upregulated in situ in treatment group (p < 0.001). In situ expression of IL-17, caspase 9, IL-23a, CxCl3 and ICAM1 showed no difference between groups (p > 0.05). Findings suggest ATG administered to donors may ameliorate the IRI process in kidney transplantation, expressed by lower necrosis and apoptosis scores and the improvement of renal function, which may be explained through the diminished in situ expression of inflammatory mediators.

► In an experimental renal transplant model we administered ATG to donor rats. ► In rATG group, lower urea and creatinine levels, necrosis and apoptosis scores ► In rATG group, lower expressions of TNFalpha, IL6, IL21, TGFbeta1, KIM1, Caspase 8 ► In rATG group, Bcl2 and HO1 were upregulated in situ. ► Results suggest preconditioning donors with rATG may ameliorate IRI.

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