Correlation of morphological findings with functional reserve in the aging donor: role of the poly (ADP-ribose) polymerase

Abstract

IntroductionThe enzyme poly (ADP-ribose) polymerase (PARP-1) participates in the first events of DNA repair in higher organisms. Under conditions of tissue ischemia, this action can lead to significant decreases in NAD(+), massive adenosine triphosphate (ATP) depletion, and cell death. In renal grafts with pretransplantation cold ischemia and subsequent ischemia-reperfusion injury, overactivation of PARP-1 may lead to a higher index of acute tubular necrosis, a delay in total recovery of the function of the transplanted organ, and an early progression to chronic graft nephropathy. The present study examined whether increased tubular expression of PARP-1 in kidneys from aged donors contributed to recipient renal function. Material and methodWe studied the nuclear expression of PARP-1 using immunohistochemistry with monoclonal antibody PAR01 in 75 kidney biopsy specimens from 40 aged donors. ResultsImmunohistochemical expression of PARP-1 showed a statistically significant relationship with donor age (r = .408, P = .006, Spearman test), with time required to achieve effective diuresis (r = .386, P = .01, Spearman test) and with creatinine levels in the first 3 months. We also highlighted a greater intensity of PARP-1 expression in suboptimal donor kidneys that failed to reduce the serum creatinine levels to <1.7 mg/dL (creatinine <1.7 PARP: 1.29 ± 1.49 vs creatinine >1.7 PARP: 2.29 ± 1.33, P = .047, Mann-Whitney U test). ConclusionWe conclude that the determination of PARP-1 in biopsy specimens from aged donors may be a useful predictive factor for renal graft function.