title: Role of poly-(ADP-ribose) polymerase in transplant acute tubular necrosis and its relationship with delayed renal function.
abstract: The enzyme poly(ADP-ribose) polymerase (PARP-1) participates in the repair of DNA damaged by genotoxic agents such as oxygen-derived free radicals. If the allograft suffers pretransplant cold ischemia and subsequent ischemia-reperfusion injury (IR), overactivation of PARP-1 can be induced, which may lead to an increase in acute tubular necrosis (ATN) and a delay in total recovery of renal function (RRF) of the transplanted organ. We studied the nuclear expression of PARP-1 in tubular cells by immunohistochemistry with the monoclonal antibody PAR01 in 104 kidney transplant biopsies from allografts with ATN. In 50% of biopsies with ATN, >50% of tubular nuclei were PARP-1+; only 9.6% of biopsies were negative. The increase in the immunohistochemical expression of PARP-1 showed a statistically significant relationship with the duration of cold ischemia, with serum creatinine levels, and with the time required to achieve effective diuresis (P < .0001, Spearman test). Cold ischemia of >24 hours and serum creatinine levels >1.7 mg/dL showed a statistically significant relationship with the highest PARP-1 expression levels (2.83 +/- 0.4 vs 1.36 +/- 0.8, P < .0001, Mann-Whitney U test). We conclude that PARP-1 plays an important role in ATN and RRF and is related to the extent and severity of ATN and to the renal allograft function.
authors.affiliation: Department of Pathology, San Cecilio University Hospital and School of Medicine, University of Granada, Granada, Spain.
authors.forename: F
authors.initials: F
authors.lastname: O'Valle
authors.forename: M C
authors.initials: MC
authors.lastname: Benítez
authors.forename: M
authors.initials: M
authors.lastname: Gómez-Morales
authors.forename: J
authors.initials: J
authors.lastname: Bravo
authors.forename: A
authors.initials: A
authors.lastname: Osuna
authors.forename: R M G
authors.initials: RM
authors.lastname: Del Moral
authors.forename: D
authors.initials: D
authors.lastname: Martín-Oliva
authors.forename: F J
authors.initials: FJ
authors.lastname: Oliver
authors.forename: R G
authors.initials: RG
authors.lastname: Del Moral
mesh_terms: D000208:Acute Disease; D001706:Biopsy; D002102:Cadaver; D004260:DNA Repair; D004231:Diuresis; D006084:Graft Rejection / Q000453:epidemiology; D006801:Humans; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology*; D007684:Kidney Tubules / Q000473:pathology*; D019520:Living Donors; D009336:Necrosis; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D012189:Retrospective Studies; D014019:Tissue Donors; D014184:Transplantation, Homologous
chemical_list: C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases