Drury Erika R, Zsengeller Zsuzsanna K, Stillman Isaac E, Khankin Eliyahu V, Pavlakis Martha, Parikh Samir M
Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts, USA.
Nephron. 2018;138(4):303-309. doi: 10.1159/000485663. Epub 2017 Dec 21.
Delayed renal graft function (DGF) contributes to the determination of length of hospitalization, risk of acute rejection, and graft loss. Existing tools aid the diagnosis of specific DGF etiologies such as antibody-mediated rejection, but markers of recovery have been elusive. The peroxisome proliferator gamma co-activator-1-alpha (PGC1α) is highly expressed in the renal tubule, regulates mitochondrial biogenesis, and promotes recovery from experimental acute kidney injury.
We aimed to determine the association between renal allograft PGC1α expression and recovery from delayed graft function.
We retrospectively analyzed patients undergoing renal transplantation at a single center from January 1, 2008 to June 30, 2014. PGC1α expression was assessed by immunostaining and ultrastructural characteristics by transmission electron microscopy. Of 34 patients who underwent renal biopsy for DGF within 30 days of transplant, 21 were included for analysis.
Low PGC1α expression was associated with a significantly longer time on dialysis after transplant (median of 35.5 vs. 16 days, p < 0.05) and a significantly higher serum creatinine (sCr) at 4 weeks after transplantation among those who discontinued dialysis (5 vs. 1.65 mg/dL, p < 0.0001). Low PGC1α expression was not associated with higher sCr at 12 weeks after transplantation. Ultrastructural characteristics including apical membrane blebbing and necrotic luminal debris were not informative regarding clinical outcomes.
These data suggest that higher PGC1α expression is associated with faster and more complete recovery from DGF. Mitochondrial biogenesis may be a therapeutic target for DGF. Larger studies are needed to validate these findings.
移植肾延迟功能恢复（DGF）影响住院时间、急性排斥反应风险和移植肾丢失。现有工具有助于诊断特定的DGF病因，如抗体介导的排斥反应，但恢复的标志物一直难以确定。过氧化物酶体增殖物激活受体γ共激活因子-1α（PGC1α）在肾小管中高表达，调节线粒体生物合成，并促进实验性急性肾损伤的恢复。
我们旨在确定移植肾PGC1α表达与移植肾功能延迟恢复之间的关联。
我们回顾性分析了2008年1月1日至2014年6月30日在单一中心接受肾移植的患者。通过免疫染色评估PGC1α表达，并通过透射电子显微镜评估超微结构特征。在移植后30天内接受DGF肾活检 的34例患者中，21例纳入分析。
PGC1α低表达与移植后透析时间显著延长相关（中位数35.5天对16天，p<0.05），在停止透析的患者中，移植后4周时血清肌酐（sCr）显著升高（5对1.65mg/dL，p<0.0001）。PGC1α低表达与移植后12周时较高的sCr无关。包括顶端膜泡形成和坏死管腔碎片在内的超微结构特征对临床结果无提示作用。
这些数据表明，较高的PGC1α表达与DGF更快、更完全的恢复相关。线粒体生物合成可能是DGF的治疗靶点。需要更大规模的研究来验证这些发现。
