Poly[ADP-ribose] polymerase-1 expression is related to cold ischemia, acute tubular necrosis, and delayed renal function in kidney transplantation.
Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN).


METHODS
Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls) and in murine Parp-1 knockout model of IR injury.


RESULTS
PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603), time to effective diuresis (r = 0.770), serum creatinine levels at biopsy (r = 0.649), and degree of ATN (r = 0.810) (p = 0.001, Pearson test). In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function.
Department of Pathology, School of Medicine, University of Granada, Granada, Spain. fovalle@ugr.es
Francisco
F
O'Valle
Raimundo G M
RG
Del Moral
María del Carmén
Mdel C
Benítez
David
D
Martín-Oliva
Mercedes
M
Gómez-Morales
David
D
Aguilar
José
J
Aneiros-Fernández
Pedro
P
Hernández-Cortés
Antonio
A
Osuna
Francesc
F
Moreso
Daniel
D
Serón
Francisco J
FJ
Oliver
Raimundo G
RG
Del Moral
D000208:Acute Disease; D000818:Animals; D001706:Biopsy; D003080:Cold Temperature; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007511:Ischemia / Q000473:pathology*; D007668:Kidney / Q000473:pathology*; D007677:Kidney Function Tests; D016030:Kidney Transplantation / Q000009:adverse effects / Q000379:methods*; D007684:Kidney Tubules / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009336:Necrosis / Q000473:pathology*; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis*
D011065:Poly(ADP-ribose) Polymerases