Role of poly-(ADP-ribose) polymerase in transplant acute tubular necrosis and its relationship with delayed renal function.
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.
O'Valle
F
F
Department of Pathology, San Cecilio University Hospital and School of Medicine, University of Granada, Granada, Spain.
Benítez
M C
MC
Gómez-Morales
M
M
Bravo
J
J
Osuna
A
A
Del Moral
R M G
RM
Martín-Oliva
D
D
Oliver
F J
FJ
Del Moral
R G
RG
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
C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases