title: Rabbit anti-rat thymocyte immunoglobulin preserves renal function during ischemia/reperfusion injury in rat kidney transplantation.
abstract: Ischemia/reperfusion (I/R) injury is an important cause of renal graft dysfunction in humans. Increases in cold and warm ischemia times lead to a higher risk of early post-transplant complications including delayed graft function and acute rejection. Moreover, prolonged cold ischemia is a predictor of long-term kidney graft loss. The protective effect of rabbit anti-rat thymocyte immunoglobulin (rATG) was evaluated in a rat model of I/R injury following syngeneic kidney transplantation. Serum creatinine concentration was evaluated at 16 h and 24 h post-transplant. Animals were sacrificed 24 h post-transplant for evaluation of histology, infiltrating leukocytes, nitrotyrosine staining, and apoptosis. rATG was effective in preventing renal function impairment, tissue damage and tubular apoptosis associated with I/R only when was given 2 h before transplantation but not at the time of reperfusion. Pretransplant rATG treatment of recipient animals effectively reduced the amount of macrophages, CD4(+), CD8(+) T cells and LFA-1(+) cells infiltrating renal graft subjected to cold ischemia as well as granzyme-B expression within ischemic kidney. On the other hand, granulocyte infiltration and oxidative stress were not modified by rATG. If these results will be translated into the clinical setting, pretransplant administration of Thymoglobuline(®) could offer the additional advantage over peri-transplant administration of limiting I/R-mediated kidney graft damage.
authors.affiliation: Transplant Research Center, Chiara Cucchi De Alessandri & Gilberto Crespi, Mario Negri Institute for Pharmacological Research, Ranica, Bergamo, Italy.
authors.forename: Sistiana
authors.initials: S
authors.lastname: Aiello
authors.forename: Paola
authors.initials: P
authors.lastname: Cassis
authors.forename: Marilena
authors.initials: M
authors.lastname: Mister
authors.forename: Samantha
authors.initials: S
authors.lastname: Solini
authors.forename: Federica
authors.initials: F
authors.lastname: Rocchetta
authors.forename: Mauro
authors.initials: M
authors.lastname: Abbate
authors.forename: Elena
authors.initials: E
authors.lastname: Gagliardini
authors.forename: Ariela
authors.initials: A
authors.lastname: Benigni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Remuzzi
authors.forename: Marina
authors.initials: M
authors.lastname: Noris
mesh_terms: D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology; D053804:Granzymes / Q000494:pharmacology; D007136:Immunoglobulins / Q000378:metabolism*; D007511:Ischemia / Q000473:pathology; D007668:Kidney / Q000378:metabolism*; D016030:Kidney Transplantation / Q000379:methods*; D008297:Male; D008856:Microscopy, Fluorescence / Q000379:methods; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000378:metabolism*; D060168:Thymocytes / Q000166:cytology*
chemical_list: D007136:Immunoglobulins; D053804:Granzymes