Poly(ADP-ribose) polymerase expression in kidney transplantation: from alfa (alpha) to Omega (Omega).
BACKGROUND
Overactivation of the enzyme poly(ADP-ribose) polymerase (PARP-1) can be induced by ischemia-reperfusion and involved in the renal injury subsequent to kidney transplant. The poly(ADP-ribosy)lation mechanism alters free radical-induced DNA damage, which is repair by PARP-1 polymer. However, PARP-1 overexpression induces cellular necrosis. Our aim was to study the immunohistochemical PARP-1 expression in kidney transplant biopsies associated with various events.


METHODS
We studied the nuclear expression of PARP-1 in kidney tubule cells by immunohistochemistry using the monoclonal antibody PAR01 in donor biopsies without acute tubular necrosis (ATN) (n = 60; controls), allografts that suffer ATN (n = 90) or an episode of acute humoral rejection (n = 12) or acute tubulointerstitial rejection (n = 25), or chronic allograft nephropathy (n = 25). Furthermore, we also studied protocol biopsies with subclinical rejection (n = 60). Renal lesions in transplant biopsies were graded blindly using 1997 Banff criteria without any clinical information.


RESULTS
Biopsies without morphological features of ATN, namely acute tubulointerstitial rejection, borderline or subclinical rejection, showed lesser PARP-1 expression compared with biopsies with ATN or with ischemic mechanism of acute humoral rejection or chronic allograft nephropathys. We observed an inverse relation between PARP-1 expression and renal function (P < .001). Overall, renal biopsies showing ATN revealed greater expression of PARP-1 (r = 0.785, Pearson test). A significant relationship with PARP-1 expression was demonstrated with renal function (effective diuresis, serum creatinine levels) and pretransplant cold ischemia time (P < .001).


CONCLUSIONS
Kidney transplant events including ischemia were associated with the highest PARP-1 expression and worse allograft renal function.
O'Valle
F
F
IBIMER and Department of Pathology, San Cecilio University Hospital and School of Medicine, University of Granada, Granada, Spain. fovalle@ugr.es
Gómez-Morales
M
M
Del Moral
R M G
RM
Serón
D
D
Moreso
F
F
Osuna
A
A
Oliver
F J
FJ
Del Moral
R G
RG
D000328:Adult; D000368:Aged; D001706:Biopsy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007511:Ischemia / Q000201:enzymology / Q000473:pathology; D016030:Kidney Transplantation / Q000473:pathology / Q000502:physiology*; D007684:Kidney Tubules / Q000201:enzymology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009336:Necrosis; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D012079:Renal Circulation; D016896:Treatment Outcome
C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases