title: Donor preconditioning with rabbit anti-rat thymocyte immunoglobulin ameliorates ischemia reperfusion injury in rat kidney transplantation.
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±8mg/dl vs. treatment: 110±15mg/dl, p<0.001; creatinine: control: 4.6±0.24mg/dl vs. treatment: 2.6±0.22mg/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.
authors.affiliation: Universidad Nacional de La Plata, La Plata, Argentina. fcicora5@gmail.com
authors.forename: Federico
authors.initials: F
authors.lastname: Cicora
authors.forename: Javier
authors.initials: J
authors.lastname: Roberti
authors.forename: Natalia
authors.initials: N
authors.lastname: Lausada
authors.forename: Pedro
authors.initials: P
authors.lastname: González
authors.forename: Diego
authors.initials: D
authors.lastname: Guerrieri
authors.forename: Pablo
authors.initials: P
authors.lastname: Stringa
authors.forename: Paola
authors.initials: P
authors.lastname: Cicora
authors.forename: Daniela
authors.initials: D
authors.lastname: Vásquez
authors.forename: Ivana
authors.initials: I
authors.lastname: González
authors.forename: Gustavo
authors.initials: G
authors.lastname: Palti
authors.forename: Dante
authors.initials: D
authors.lastname: Intile
authors.forename: Clemente
authors.initials: C
authors.lastname: Raimondi
mesh_terms: D000818:Animals; D000961:Antilymphocyte Serum / Q000008:administration & dosage*; D017209:Apoptosis; D053181:Caspase 8 / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003404:Creatinine / Q000032:analysis; D020869:Gene Expression Profiling; D019254:Genes, bcl-2; D051547:Heme Oxygenase-1 / Q000235:genetics; D015850:Interleukin-6 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007668:Kidney / Q000276:immunology; D016030:Kidney Transplantation; D008297:Male; D009336:Necrosis; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000517:prevention & control*; D060168:Thymocytes / Q000276:immunology*; D014019:Tissue Donors; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation; D014508:Urea / Q000032:analysis; D000098546:Interleukin-21
chemical_list: D000961:Antilymphocyte Serum; D053181:Caspase 8; D015815:Cell Adhesion Molecules; D003404:Creatinine; D051547:Heme Oxygenase-1; D015850:Interleukin-6; D007378:Interleukins; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D014508:Urea; D000098546:Interleukin-21; C110936:Havcr1 protein, rat; C505528:Casp8 protein, rat