Hazama Takuma, Fukami Kei, Yamagishi Sho-ichi, Kusumoto Takuo, Sakai Kazuko, Adachi Takeki, Sonoda Kazuhiro, Kasuga Syumon, Ueda Seiji, Okuda Seiya
Division of Nephrology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Ther Apher Dial. 2014 Oct;18(5):391-7. doi: 10.1111/1744-9987.12120. Epub 2013 Nov 20.
Peritoneal protein loss due to high peritoneal permeability may contribute to hypoalbuminemia and early withdrawal from peritoneal dialysis (PD) therapy in end stage renal disease (ESRD) patients. We have found that pigment epithelium-derived factor (PEDF) has anti-vasopermeability properties both in cell culture and animal models by counteracting the biological actions of vascular endothelial growth factor (VEGF). However, it remains unknown which clinical variables, including dialysate VEGF and PEDF, are associated with decreased serum albumin levels and could predict early withdrawal from the PD in ESRD patients. We address these issues. Twenty-seven ESRD patients undergoing PD were enrolled. Clinical variables were measured at 6 months after commencing PD. We examined the independent correlates of serum albumin in PD patients and then prospectively investigated the predictors of withdrawal from the PD therapy over 4 years. Dialysate VEGF was associated with peritoneal solute transport rate (P = 0.002), serum albumin (inversely, P < 0.001) and dialysate PEDF levels (P < 0.001). In multiple stepwise regression analysis, age (P = 0.002) and dialysate VEGF levels (P < 0.001) were independent determinants of serum albumin levels. High VEGF (>27 pg/mL), low serum albumin (≤ 3.31 g/dL) and low hemoglobin (≤ 11.2 g/dL) were correlated with withdrawal from the PD therapy during the 4 years. The odds ratio of dialysate VEGF for early withdrawal from the PD was 6.310 (P = 0.035). The present study demonstrated that increased dialysate VEGF was associated with decreased serum albumin and early withdrawal from the PD therapy. Inhibition of peritoneal VEGF production may be a therapeutic target in PD patients.
由于腹膜通透性高导致的腹膜蛋白丢失可能会促使终末期肾病（ESRD）患者出现低白蛋白血症，并导致其早期退出腹膜透析（PD）治疗。我们发现，色素上皮衍生因子（PEDF）在细胞培养和动物模型中均具有抗血管通透性特性，其作用机制是抵消血管内皮生长因子（VEGF）的生物学作用。然而，包括透析液VEGF和PEDF在内的哪些临床变量与血清白蛋白水平降低相关，以及能否预测ESRD患者早期退出PD治疗，目前仍不清楚。我们针对这些问题展开了研究。招募了27例接受PD治疗的ESRD患者。在开始PD治疗6个月后测量临床变量。我们研究了PD患者血清白蛋白的独立相关因素，然后前瞻性地调查了4年期间退出PD治疗的预测因素。透析液VEGF与腹膜溶质转运率相关（P = 0.002）、与血清白蛋白相关（呈负相关，P < 0.001）以及与透析液PEDF水平相关（P < 0.001）。在多元逐步回归分析中，年龄（P = 0.002）和透析液VEGF水平（P < 0.001）是血清白蛋白水平的独立决定因素。高VEGF（>27 pg/mL）、低血清白蛋白（≤ 3.31 g/dL）和低血红蛋白（≤ 11.2 g/dL）与4年期间退出PD治疗相关。透析液VEGF导致早期退出PD治疗的比值比为6.310（P = 0.035）。本研究表明，透析液VEGF升高与血清白蛋白降低及早期退出PD治疗相关。抑制腹膜VEGF生成可能是PD患者的一个治疗靶点。
