Liu Yu-Hsien, Chen Yu-Hsuan, Ko Chi-Hua, Kuo Chia-Wen, Yen Chih-Ching, Chen Wei, Chong Kowit-Yu, Chen Chuan-Mu
Department of Life Sciences, Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 402, Taiwan.
Department of Internal Medicine, Jen-Ai Hospital, Dali Branch, Taichung 402, Taiwan.
Antioxidants (Basel). 2022 Jun 18;11(6):1198. doi: 10.3390/antiox11061198.
End-stage renal disease (ESRD) patients experience oxidative stress due to excess exogenous or endogenous oxidants and insufficient antioxidants. Hence, oxidative stress and inflammation cause endothelial damage, contributing to vascular dysfunction and atherosclerosis. Therefore, ESRD patients suffer more cardiovascular and hospitalization events than healthy people. This study aims to test the correlations between ROS, SOD3, IL-2, IL-6, and IL-18 and the first kidney disease-related hospitalization or death events in ESRD patients undergoing regular hemodialysis. A total of 212 participants was enrolled, including 45 normal healthy adults and 167 ESRD patients on regular dialysis. Blood samples from all participants were collected for ROS, SOD3, IL-2, IL-6, and IL-18 measurement at the beginning of the study, and every kidney disease-related admission or death was recorded for the next year. Multivariate analysis was conducted by fitting a linear regression model, logistic regression model, and Cox proportional hazards model to estimate the adjusted effects of risk factors, prognostic factors, or predictors on continuous, binary, and survival outcome data. The results showed that plasma SOD3 and serum IL-18 were two strong predictors of the first kidney disease-related hospitalization or death. In the Cox proportional hazards models (run in R), higher IL-18 concentration (>69.054 pg/mL) was associated with a hazard ratio of 3.376 for the first kidney disease-related hospitalization or death (95% CI: 1.2644 to 9.012), while log(SOD3) < 4.723 and dialysis clearance (Kt/V; 1.11 < value < 1.869) had a hazard ratio = 0.2730 (95% CI: 0.1133 to 0.6576) for reducing future kidney disease-related hospitalization or death. Other markers, including body mass index (BMI), transferrin saturation, total iron binding capacity, and sodium and alkaline phosphate, were also found to be significant in our study. These results reveal the new predictors SOD3 and IL-18 for the medical care of end-stage renal disease patients.
终末期肾病（ESRD）患者由于外源性或内源性氧化剂过多以及抗氧化剂不足而经历氧化应激。因此，氧化应激和炎症会导致内皮损伤，进而导致血管功能障碍和动脉粥样硬化。所以，ESRD患者比健康人更容易发生心血管事件和住院。本研究旨在测试接受定期血液透析的ESRD患者中活性氧（ROS）、超氧化物歧化酶3（SOD3）、白细胞介素-2（IL-2）、白细胞介素-6（IL-6）和白细胞介素-18（IL-18）与首次肾病相关住院或死亡事件之间的相关性。总共招募了212名参与者，包括45名正常健康成年人和167名接受定期透析的ESRD患者。在研究开始时收集所有参与者的血样以测量ROS、SOD3、IL-2、IL-6和IL-18，并记录下一年每例肾病相关的入院或死亡情况。通过拟合线性回归模型、逻辑回归模型和Cox比例风险模型进行多变量分析，以估计风险因素、预后因素或预测因素对连续、二元和生存结局数据的调整效应。结果表明，血浆SOD3和血清IL-18是首次肾病相关住院或死亡的两个强有力的预测指标。在Cox比例风险模型（在R中运行）中，较高的IL-18浓度（>69.054 pg/mL）与首次肾病相关住院或死亡的风险比为3.376（95%置信区间：1.2644至9.012），而log(SOD3)<4.723和透析清除率（Kt/V；1.11<值<1.869）降低未来肾病相关住院或死亡的风险比=0.2730（95%置信区间：0.1133至0.6576）。其他指标，包括体重指数（BMI）、转铁蛋白饱和度、总铁结合能力以及钠和碱性磷酸酶，在我们的研究中也被发现具有显著性。这些结果揭示了用于终末期肾病患者医疗护理的新预测指标SOD3和IL-18。
