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间皮细胞的上皮-间质转化是腹膜透析过程中的早期事件,且与高腹膜转运相关。

Epithelial-to-mesenchymal transition of mesothelial cells is an early event during peritoneal dialysis and is associated with high peritoneal transport.

作者信息

Del Peso G, Jiménez-Heffernan J A, Bajo M A, Aroeira L S, Aguilera A, Fernández-Perpén A, Cirugeda A, Castro M J, de Gracia R, Sánchez-Villanueva R, Sánchez-Tomero J A, López-Cabrera M, Selgas R

机构信息

Servicio de Nefrología y Unidad de Investigación, Hospital Universitario La Paz, Red Renal de Investigación Cooperativa , Madrid, Spain.

出版信息

Kidney Int Suppl. 2008 Apr(108):S26-33. doi: 10.1038/sj.ki.5002598.

Abstract

Ultrafiltration (UF) failure is a consequence of long-term peritoneal dialysis (PD). Fibrosis, angiogenesis, and vasculopathy are causes of this functional disorder after 3-8 years on PD. Epithelial-to-mesenchymal transition (EMT) of mesothelial cell (MC) is a key process leading to peritoneal fibrosis with functional deterioration. Our purpose was to study the peritoneal anatomical changes during the first months on PD, and to correlate them with peritoneal functional parameters. We studied 35 stable PD patients for up to 2 years on PD, with a mean age of 45.3+/-14.5 years. Seventy-four percent of patients presented loss of the mesothelial layer, 46% fibrosis (>150 microm) and 17% in situ evidence of EMT (submesothelial cytokeratin staining), which increased over time. All patients with EMT showed myofibroblasts, while only 36% of patients without EMT had myofibroblasts. The number of peritoneal vessels did not vary when we compared different times on PD. Vasculopathy was present in 17% of the samples. Functional studies were used to define the peritoneal transport status. Patients in the highest quartile of mass transfer area coefficient of creatinine (Cr-MTAC) (>11.8 ml min(-1)) showed significantly higher EMT prevalence (P=0.016) but similar number of peritoneal vessels. In the multivariate analysis, the highest quartile of Cr-MTAC remained as an independent factor predicting the presence of EMT (odds ratio 12.4; confidence interval: 1.6-92; P=0.013) after adjusting for fibrosis (P=0.018). We concluded that, during the first 2 PD years, EMT of MCs is a frequent morphological change in the peritoneal membrane. High solute transport status is associated with its presence but not with increased number of peritoneal vessels.

摘要

超滤失败是长期腹膜透析(PD)的一个后果。纤维化、血管生成和血管病变是PD治疗3 - 8年后这种功能障碍的原因。间皮细胞(MC)的上皮 - 间充质转化(EMT)是导致腹膜纤维化并伴有功能恶化的关键过程。我们的目的是研究PD治疗最初几个月期间的腹膜解剖学变化,并将其与腹膜功能参数相关联。我们研究了35例稳定的PD患者,PD治疗时间长达2年,平均年龄为45.3±14.5岁。74%的患者出现间皮层缺失,46%出现纤维化(>150微米),17%有原位EMT证据(间皮下细胞角蛋白染色),且随时间增加。所有有EMT的患者均显示有肌成纤维细胞,而无EMT的患者中只有36%有肌成纤维细胞。当我们比较PD不同时间时,腹膜血管数量没有变化。17%的样本存在血管病变。功能研究用于定义腹膜转运状态。肌酐质量转移面积系数(Cr - MTAC)处于最高四分位数(>11.8 ml min⁻¹)的患者显示EMT患病率显著更高(P = 0.016),但腹膜血管数量相似。在多变量分析中,调整纤维化因素(P = 0.018)后,Cr - MTAC的最高四分位数仍然是预测EMT存在的独立因素(优势比12.4;置信区间:1.6 - 92;P = 0.013)。我们得出结论,在PD治疗的前2年,MC的EMT是腹膜的一种常见形态学变化。高溶质转运状态与其存在相关,但与腹膜血管数量增加无关。

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