Association of Serum Paraoxonase/Arylesterase Activity With All-Cause Mortality in Maintenance Hemodialysis Patients

Context: In end-stage renal disease (ESRD), serum high-density lipoprotein cholesterol (HDL-C) level is not an accurate predictor of mortality, partly because it does not necessarily correlate with indices of HDL function. Paraoxonase (PON) is a major enzyme constituent of HDL and key component of HDL antioxidant activity. Apolipoprotein (Apo) A-I is the core HDL structural protein that plays a major role in various aspects of HDL function. Objective: We sought to examine PON activity and Apo A-I levels in patients with ESRD vs healthy controls. Design and Setting: PON/Arylesterase activity was measured in 499 patients with maintenance hemodialysis (MHD) and 24 healthy controls with similar distributions of age, sex and race/ethnicity. Serum acrolein-modified Apo A-I was measured in 30 patients with MHD and 10 healthy controls. Main Outcome Measures: Multilevel Cox models were used to assess associations among PON activity, Apo A-I, and HDL-C levels with 12-month all-cause mortality. Results: PON activity was significantly lower in patients with MHD vs controls. Furthermore, acrolein-modified Apo A-I levels were higher in patients with MHD vs controls. In fully adjusted models, high PON activity was associated with lower 12-month mortality, whereas no difference of mortality risk was observed across HDL-C levels. The combination of high PON and low Apo A-I compared with low PON and low Apo A-I was associated with lower mortality risk. Conclusions: In patients with MHD, PON activity had a stronger association with 12-month mortality than HDL-C. Future studies are needed to examine the role of these markers as potential diagnostic and therapeutic tools in ESRD.研究背景：在终末期肾病（end-stage renal disease, ESRD）患者中，血清高密度脂蛋白胆固醇（high-density lipoprotein cholesterol, HDL-C）水平无法准确预测死亡风险，部分原因在于其未必与高密度脂蛋白功能指标相关。对氧磷酶（Paraoxonase, PON）是高密度脂蛋白的主要酶类组分，也是其抗氧化活性的关键组成部分。载脂蛋白（Apolipoprotein, Apo）A-I是高密度脂蛋白的核心结构蛋白，在该脂蛋白功能的诸多方面发挥核心作用。 研究目的：本研究旨在对比终末期肾病患者与健康对照者的对氧磷酶活性及载脂蛋白A-I水平。 研究设计与场景：本研究纳入499名维持性血液透析（maintenance hemodialysis, MHD）患者，以及24名年龄、性别、种族/族裔分布匹配的健康对照者，检测两组的对氧磷酶/芳基酯酶活性；另纳入30名维持性血液透析患者与10名健康对照者，检测其血清丙烯醛修饰的载脂蛋白A-I水平。 主要结局指标：采用多水平Cox模型评估对氧磷酶活性、载脂蛋白A-I及HDL-C水平与12个月全因死亡率的关联。 研究结果：维持性血液透析患者的对氧磷酶活性显著低于健康对照者；此外，维持性血液透析患者的血清丙烯醛修饰的载脂蛋白A-I水平显著高于健康对照者。在完全校正模型中，较高的对氧磷酶活性与更低的12个月死亡率相关，而不同HDL-C水平间的死亡风险无显著差异。与“低对氧磷酶活性+低载脂蛋白A-I水平”的组合相比，“高对氧磷酶活性+低载脂蛋白A-I水平”的组合与更低的死亡风险相关。 研究结论：在维持性血液透析患者中，对氧磷酶活性与12个月死亡率的关联强度高于HDL-C。未来仍需开展相关研究，以明确上述标志物作为终末期肾病潜在诊断及治疗工具的应用价值。