Division of Nephrology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
Center of Cancer Program Development, E-Da Cancer Hospital, I-Shou University, Kaohsiung 84001, Taiwan.
Nutrients. 2021 Mar 21;13(3):1014. doi: 10.3390/nu13031014.
Current strategies targeting serum cholesterol bring limited benefits to mortality and macrovascular events prevention among hemodialysis patients. Direct measurements and analysis on circulating markers of cholesterol homeostasis could be promising solutions to this bottleneck. We prospectively enrolled 90 maintenance hemodialysis patients and 9 healthy controls in 2019 for 1 year. We measured circulating desmosterol and lathosterol as markers for cholesterol synthesis and campesterol and sitosterol for cholesterol absorption. At baseline, hemodialysis patients showed higher levels of campesterol ( = 0.023) compared to healthy controls. During follow-up, we identified 14 (15.4%) patients who experienced macrovascular events. Comparisons of cholesterol homeostasis markers between cohorts with and without macrovascular events showed no significant differences in markers of cholesterol synthesis or absorption. Using logistic regression analysis, the odds ratio was not statistically significant for the prediction of macrovascular events after full-adjusting for age, sex, diabetes, serum albumin, cholesterol, and triglyceride. We concluded that hemodialysis patients demonstrated higher level of cholesterols absorption, indicated by circulating campesterol compared to healthy subjects. Markers for cholesterol homeostasis were not significantly associated with macrovascular events during a 1-year follow-up. Our results shed light on the novel therapeutic target of modulating cholesterol absorption in HD patients.
目前针对血清胆固醇的治疗策略在降低血液透析患者死亡率和大血管事件方面的获益有限。直接测量和分析胆固醇稳态的循环标志物可能是解决这一瓶颈的有前途的方法。我们在 2019 年前瞻性地招募了 90 名维持性血液透析患者和 9 名健康对照者进行了为期 1 年的随访。我们测量了循环中的羊毛固醇和菜油固醇作为胆固醇合成的标志物,以及谷固醇和豆固醇作为胆固醇吸收的标志物。在基线时,血液透析患者的谷固醇水平(= 0.023)高于健康对照组。在随访期间,我们确定了 14 名(15.4%)发生大血管事件的患者。对有和无大血管事件的队列进行胆固醇稳态标志物比较,在胆固醇合成或吸收标志物方面没有显著差异。使用逻辑回归分析,在充分调整年龄、性别、糖尿病、血清白蛋白、胆固醇和甘油三酯后,大血管事件的预测中,胆固醇比值无统计学意义。我们的结论是,与健康受试者相比,血液透析患者的胆固醇吸收水平更高,表现为循环中的谷固醇水平升高。在 1 年的随访中,胆固醇稳态标志物与大血管事件之间没有显著相关性。我们的研究结果为在 HD 患者中调节胆固醇吸收这一新型治疗靶点提供了启示。