O'Valle F, Benítez M C, Gómez-Morales M, Bravo J, Osuna A, Martin-Oliva D, Oliver F J, Del Moral R G
Department of Pathology, San Cecilio University Hospital and School of Medicine, University of Granada, Spain.
Transplant Proc. 2005 Nov;37(9):3684-7. doi: 10.1016/j.transproceed.2005.09.109.
Kidney allografts undergo pretransplant cold ischemia and consequent ischemia-reperfusion injury (IR). Poly (ADP-Ribose) polymerase (PARP-1) overactivation leads to massive NAD+ consumption and ATP depletion with induction of cellular necrosis under ischemic conditions, which may lead to an increase in acute tubular necrosis (ATN) and a delay in total recovery of renal function (RFR) of the transplanted organ.
Nuclear PARP-1 immunohistochemical expression (clone: PARP01) was studied in 155 paraffin-embedded renal biopsies from suboptimal donors and 95 kidney allograft biopsies with histopathological diagnosis of ATN.
In 50% of ATN biopsies, more than 50% of tubular nuclei were immunostained for PARP-1. PARP-1 expression was higher in ATN biopsies than in those from suboptimal donors (2.40 +/- 0.74 vs 0.92 +/- 1.13, P = 0.0001 Mann-Whitney). PARP-1 showed a statistically significant relationship with the time required to achieve effective diuresis (Rho:0.779), with serum creatinine, and with duration of cold ischemia (Rho:0.803). These relationships were stronger in the biopsies with ATN. In conclusion, multivariate analysis demonstrated that PARP-1 expression and cold ischemia duration in kidney biopsies with ATN predicted the short-term delay in total recovery of renal function and serum creatinine in the first month.
肾移植受者经历移植前冷缺血及随之而来的缺血再灌注损伤(IR)。聚(ADP - 核糖)聚合酶(PARP - 1)过度激活会导致大量烟酰胺腺嘌呤二核苷酸(NAD⁺)消耗和三磷酸腺苷(ATP)耗竭,并在缺血条件下诱导细胞坏死,这可能导致急性肾小管坏死(ATN)增加以及移植器官肾功能完全恢复(RFR)延迟。
在155例来自边缘供体的石蜡包埋肾活检组织以及95例组织病理学诊断为ATN的肾移植活检组织中,研究了核PARP - 1免疫组化表达(克隆:PARP01)。
在50%的ATN活检组织中,超过50%的肾小管细胞核被PARP - 1免疫染色。PARP - 1在ATN活检组织中的表达高于边缘供体的活检组织(2.40±0.74对0.92±1.13,P = 0.0001,曼 - 惠特尼检验)。PARP - 1与实现有效利尿所需时间(Rho:0.779)、血清肌酐以及冷缺血持续时间(Rho:0.803)呈统计学显著相关。在ATN活检组织中这些相关性更强。总之,多变量分析表明,ATN肾活检组织中的PARP - 1表达和冷缺血持续时间可预测移植后第一个月肾功能完全恢复和血清肌酐的短期延迟。