The importance of paraoxonase 1 activity in chronic kidney disease

Paraoxonase 1 (PON1) is one of the most significant antioxidative enzymes associated with high-density lipoprotein (HDL). It has been proved that is involved in the pathogenesis of many diseases including chronic kidney disease (CKD). The association between PON1 and CKD seems to be mutual, such that the disease produces a significant decrease in PON1 activity levels, while the genetics of PON1 may affect the risk of susceptibility to CKD. Recent studies reveal that the decrease in serum PON1 activity observed in non-dialyzed and dialyzed CKD patients as well as in renal transplant (RT) patients is linked to an increased vulnerability to atherosclerosis. We intend to summarize current literature concerning PON1 activity in CKD, highlighting on the main determinants of PON1 activity, its association with oxidative stress, the impact of its genetic polymorphism on the disease development, the effect of drugs and nutritional state. Furthermore, evidence supporting the implication of reduced PON1 activity in the incident of cardiovascular disease in CKD patients, is also examined. It appears that despite the lack of standardization of PON1 activity measurement, PON1 remains a valuable biomarker for the researchers through the last decades, which contributes to the assessment of the antioxidant status having prognostic benefit on adverse clinical outcomes at various stages and etiologies of kidney disease.

对氧磷酶1（Paraoxonase 1, PON1）是与高密度脂蛋白（high-density lipoprotein, HDL）相关的关键抗氧化酶之一。现有研究证实，该酶参与包括慢性肾脏病（chronic kidney disease, CKD）在内的多种疾病的发病进程。PON1与CKD之间的关联呈现双向性：一方面该疾病会显著降低PON1的血清活性水平，另一方面PON1的遗传学特征可影响个体罹患CKD的易感性。近期研究表明，未透析、透析的CKD患者以及肾移植（renal transplant, RT）患者体内检测到的血清PON1活性下降，与动脉粥样硬化易感性升高存在紧密关联。

本综述旨在总结当前有关CKD患者PON1活性的研究文献，重点阐述PON1活性的主要影响因素、其与氧化应激的关联、基因多态性对疾病发生的作用，以及药物与营养状态的影响。此外，本综述还将探讨支持“PON1活性降低与CKD患者心血管疾病发生相关”的相关证据。尽管目前PON1活性的检测方法尚未实现标准化，但数十年来，PON1始终是研究者们依赖的极具价值的生物标志物，可用于评估机体抗氧化状态，对不同分期、不同病因的肾脏病患者的不良临床结局具有预后评估价值。