Alvarez S, Suazo C, Boltansky A, Ursu M, Carvajal D, Innocenti G, Vukusich A, Hurtado M, Villanueva S, Carreño J E, Rogelio A, Irarrazabal C E
Transplantation Unit, Davila Clinic, Santiago, Chile.
Transplant Proc. 2013;45(10):3719-23. doi: 10.1016/j.transproceed.2013.08.079.
End-stage renal disease (ESRD) requires for its treatment permanent dialysis or kidney transplantation (KT). KT is the best clinical treatment, however, the early function of the allograft varies depending on multiple factors associated with cold ischemia time (CIT) and the allograft rejection process. It is known that serum creatinine is an insensitive and late marker for predicting graft recovery after KT, mainly in patients with delayed graft function (DGF). Neutrophil gelatinase-associated lipocalin (NGAL) is produced in the distal nephron and it is one of the most promising novel biomarkers for acute kidney injury (AKI) and chronic kidney disease (CKD). NGAL has been proposed to be a predictor of organ recovery from DGF after KT from donors after cardiac death. Because nonrenal diseases can also induce NGAL, more information is necessary to validate the sensitivity and specificity of urine and plasma NGAL in clinical samples. The exosomes are vesicles released into the urine from the kidney epithelium and they have been proposed as better source to explore as biomarker of renal dysfunction. The molecular composition of the urinary exosomes could be representative of the physiological or physiopathologic condition of the urinary system. We propose that determination of NGAL in urinary exosomes is a better predictor of kidney dysfunction after KT than other urinary fractions. We analyzed 15 kidney allograft recipients, with a mean age of 36 years (range, 16-60 years) and 75% were male: 11 living donors (LD) and 4 deceased donors (DD). The average length of CIT was 14 hours in DD and less than 1 hour in LD. Three patient developed DGF. Using Western blot analysis, NGAL was detectable in the cellular and exosomal fraction of the urine. The exosomes expressed higher levels of NGAL than the cellular fraction. The expression of NGAL was observed from the first day after transplantation. In the cellular fraction of the urine, no significant differences of NGAL were observed between the patients. However, the median of NGAL expression in the exosomes fraction was significantly higher in DD patient, from the first day after KT (P < .05). Moreover, we noticed that NGAL expression in exosomes remained elevated in the patients with DGF compared with non-DGF patients (P < .05). Considering the highest abundance of NGAL in the urinary exosomes and its correlation with DGF patients, we suggest the exosomal fraction as a more sensitive substrate to evaluate early biomarkers of DGF after KT.
终末期肾病（ESRD）的治疗需要进行长期透析或肾移植（KT）。肾移植是最佳的临床治疗方法，然而，同种异体移植肾的早期功能因与冷缺血时间（CIT）和移植肾排斥反应相关的多种因素而异。众所周知，血清肌酐是预测肾移植后移植肾恢复情况的不敏感且滞后的指标，在移植肾功能延迟（DGF）的患者中尤为如此。中性粒细胞明胶酶相关脂质运载蛋白（NGAL）在远端肾单位产生，是急性肾损伤（AKI）和慢性肾病（CKD）最有前景的新型生物标志物之一。有人提出NGAL可作为心脏死亡后供体肾移植后DGF患者移植肾恢复情况的预测指标。由于非肾脏疾病也可诱导NGAL产生，因此需要更多信息来验证临床样本中尿和血浆NGAL的敏感性和特异性。外泌体是从肾上皮细胞释放到尿液中的囊泡，有人提出外泌体是探索肾功能障碍生物标志物的更好来源。尿外泌体的分子组成可能代表泌尿系统的生理或病理生理状况。我们认为，与其他尿成分相比，测定尿外泌体中的NGAL是肾移植后肾功能障碍更好的预测指标。我们分析了15例肾移植受者，平均年龄36岁（范围16 - 60岁），75%为男性：11例活体供体（LD）和4例尸体供体（DD）。尸体供体的平均冷缺血时间为14小时，活体供体则少于1小时。3例患者发生了移植肾功能延迟。采用蛋白质印迹分析，在尿的细胞成分和外泌体成分中均可检测到NGAL。外泌体中NGAL的表达水平高于细胞成分。移植后第一天就观察到了NGAL的表达。在尿的细胞成分中，患者之间NGAL未观察到显著差异。然而，尸体供体患者肾移植后第一天，外泌体成分中NGAL表达的中位数显著更高（P < 0.05）。此外，我们注意到，与未发生移植肾功能延迟的患者相比，发生移植肾功能延迟的患者外泌体中NGAL的表达持续升高（P < 0.05）。考虑到尿外泌体中NGAL含量最高且与移植肾功能延迟患者相关，我们建议将外泌体成分作为评估肾移植后移植肾功能延迟早期生物标志物更敏感的底物。
