Tsai Yi-Chun, Chiu Yi-Wen, Kuo Hung-Tien, Lee Jia-Jung, Lee Su-Chu, Chen Tzu-Hui, Lin Ming-Yen, Hwang Shang-Jyh, Kuo Mei-Chuan, Hsu Ya-Ling, Chen Hung-Chun
Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
PLoS One. 2017 Mar 23;12(3):e0173906. doi: 10.1371/journal.pone.0173906. eCollection 2017.
Fluid overload is not only the characteristic but also an important complication in chronic kidney disease (CKD) patients. Angiopoietin-2 (Angpt2) disturbs endothelium and vessel permeability, which may induce fluid overload. The aim of this study is to examine the interaction between fluid status and Angpt2 in adverse renal outcomes of CKD.
This cohort study enrolled 290 patients with CKD stages 3-5 from January 2011 to December 2011 and followed up until December 2015. Fluid status was presented as overhydration (OH) value measured by body composition monitor, while OH>1.1L was defined as fluid overload. Renal outcomes were defined as commencing dialysis and rapid renal function decline (the slope of estimated glomerular filtration rate < -5 ml/min/1.73 m2/y).
During a mean follow-up of 38.6±18.3 months, 125 (43.1%) patients progressed to commencing dialysis and 99(34.7%) patients presented rapid renal function decline. All patients were stratified by OH of 1.1L and the median of circulating Angpt2. These patients with both OH>1.1L and high circulating Angpt2 were more likely to reach commencing dialysis compared to other groups. The risks for commencing dialysis and rapid renal function decline were significantly higher in patients with OH>1.1L and high circulating Angpt2 level compared to those with OH≦1.1L and low circulating Angpt2 (2.14, 1.21-3.78, P = 0.009; 4.96, 1.45-16.97, P = 0.01). There was a significant interaction between OH level and circulating Angpt2 in entering dialysis (P-interaction = 0.02).
Fluid overload and Angpt2 might have a synergistic effect on adverse renal outcomes in CKD patients.
液体超负荷不仅是慢性肾脏病（CKD）患者的特征，也是其重要并发症。血管生成素-2（Angpt2）会干扰内皮细胞和血管通透性，这可能会导致液体超负荷。本研究旨在探讨CKD不良肾脏结局中液体状态与Angpt2之间的相互作用。
本队列研究纳入了2011年1月至2011年12月的290例3-5期CKD患者，并随访至2015年12月。液体状态以体成分监测仪测量的水合过量（OH）值表示，OH>1.1L被定义为液体超负荷。肾脏结局定义为开始透析和肾功能快速下降（估计肾小球滤过率斜率<-5 ml/min/1.73 m²/y）。
在平均38.6±18.3个月的随访期间，125例（43.1%）患者进展至开始透析，99例（34.7%）患者出现肾功能快速下降。所有患者根据OH 1.1L和循环Angpt2中位数进行分层。与其他组相比，OH>1.1L且循环Angpt2水平高的患者更有可能开始透析。与OH≤1.1L且循环Angpt2水平低的患者相比，OH>1.1L且循环Angpt2水平高的患者开始透析和肾功能快速下降的风险显著更高（2.14，1.21-3.78，P = 0.009；4.96，1.45-16.97，P = 0.01）。在开始透析方面，OH水平与循环Angpt2之间存在显著的相互作用（交互P值 = 0.02）。
液体超负荷和Angpt2可能对CKD患者的不良肾脏结局具有协同作用。
