Gungor Ozkan, Unal Hilmi Umut, Guclu Aydin, Gezer Mustafa, Eyileten Tayfun, Guzel Fatma Betül, Altunoren Orcun, Erken Ertugrul, Oguz Yusuf, Kocyigit Ismail, Yilmaz Mahmut Ilker
Department of Nephrology, Sütçü İmam University, Kahramanmaras, Turkey.
Department of Nephrology, Gulhane School of Medicine, Ankara, Turkey.
PLoS One. 2017 Jun 14;12(6):e0178939. doi: 10.1371/journal.pone.0178939. eCollection 2017.
Increased inflammation, associated with the increase in chronic kidney disease (CKD) stage, has a very important influence in vascular injury and cardiovascular diseases. In this study, we aimed to investigate the levels of IL-33 and ST2 in the different stages of CKD and to determine their effect on vascular damage and cardiovascular events (CVE).
This was an observational cohort study in which serum IL-33 and ST2 were obtained from 238 CKD (stages 1-5) patients. We examined the changes in IL-33/ST2 levels in CKD patients, as well as the association with a surrogate of endothelial dysfunction. Fatal and non-fatal CVE were recorded for a mean of 24 months. We also performed a COX regression analysis to determine the association of IL-33/ST2 levels with CVE and survival.
IL-33 and ST2 levels were significantly increased and estimated glomerular filtration rates (eGFR) were decreased. Flow-mediated dilatation (FMD) was significantly decreased from stage 1 to stage 5 CKD. IL-33 and ST2 levels were associated with FMD, and ST2 was a predictor. Multivariate Cox analysis showed that the presence of diabetes mellitus, smoking, and proteinuria and haemoglobin, Hs-CRP, IL-33, and ST2 were associated with the risk of CVE. Kaplan-Meier survival curves showed that patients with IL-33 and ST2 levels below the median value (IL-33 = 132.6 ng/L, ST2 = 382.9 pg/mL) had a higher cumulative survival compared with patients who had IL-33 and ST2 levels above the median value (log-rank test, p = 0.000).
This is the first study that demonstrates that serum IL-33 and ST2 are associated with vascular injury, cardiovascular events, and survival in CKD patients.
炎症增加与慢性肾脏病（CKD）分期增加相关，对血管损伤和心血管疾病有疾病具有非常重要的影响。在本研究中，我们旨在调查CKD不同阶段白细胞介素-33（IL-33）和ST2的水平，并确定它们对血管损伤和心血管事件（CVE）的影响。
这是一项观察性队列研究，从238例CKD（1-5期）患者中获取血清IL-33和ST2。我们检查了CKD患者IL-33/ST2水平的变化，以及与内皮功能障碍替代指标的关联。记录平均24个月内的致命和非致命CVE。我们还进行了COX回归分析，以确定IL-33/ST2水平与CVE和生存率的关联。
IL-33和ST2水平显著升高，估计肾小球滤过率（eGFR）降低。从CKD 1期到5期，血流介导的血管舒张（FMD）显著降低。IL-33和ST2水平与FMD相关，且ST2是一个预测指标。多变量COX分析显示，糖尿病、吸烟、蛋白尿和血红蛋白、超敏C反应蛋白（Hs-CRP）、IL-33和ST2与CVE风险相关。Kaplan-Meier生存曲线显示，IL-33和ST2水平低于中位数（IL-33 = 132.6 ng/L，ST2 = 382.9 pg/mL）的患者与IL-33和ST2水平高于中位数的患者相比，累积生存率更高（对数秩检验，p = 0.000）。
这是第一项表明血清IL-33和ST与CKD患者血管损伤、心血管事件和生存率相关的研究。
