Department of Biochemistry, "Alexandra" Hospital, Athens, Greece.
Renal Unit, "Aretaeio" Hospital, Athens, Greece.
Ren Fail. 2024 Dec;46(2):2376930. doi: 10.1080/0886022X.2024.2376930. Epub 2024 Jul 10.
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(PON1)是与高密度脂蛋白(HDL)相关的最重要的抗氧化酶之一。已经证明,它与许多疾病的发病机制有关,包括慢性肾脏病(CKD)。PON1 与 CKD 之间的关系似乎是相互的,即该疾病会导致 PON1 活性水平显著降低,而 PON1 的遗传可能会影响 CKD 的易感性风险。最近的研究表明,在非透析和透析 CKD 患者以及肾移植(RT)患者中观察到的血清 PON1 活性降低与动脉粥样硬化的易感性增加有关。我们旨在总结关于 CKD 中 PON1 活性的当前文献,重点介绍 PON1 活性的主要决定因素、其与氧化应激的关系、其遗传多态性对疾病发展的影响、药物和营养状态的影响。此外,还检查了支持 PON1 活性降低与 CKD 患者心血管疾病发生的证据。尽管 PON1 活性的测量缺乏标准化,但在过去的几十年中,PON1 仍然是研究人员的有价值的生物标志物,有助于评估抗氧化状态,对各种阶段和病因的肾脏疾病的不良临床结局具有预后益处。