Paraoxonase 1 and Chronic Kidney Disease: A Meta-Analysis

Abstract

Oxidative stress is known to be associated with the pathophysiology of chronic kidney disease (CKD). Paraoxonase 1 (PON1) is an antioxidant enzyme that has been proposed as a biomarker for CKD. While several studies have reported an association between serum PON1 activity and CKD, consensus based on systematically analyzed data remains necessary. We set out to conduct a meta-analysis of literature on PON1 in CKD. Electronic databases, such as MEDLINE, Embase and CENTRAL, were searched for available studies on PON1 activity in patients with CKD (without dialysis) as published before December 2022. A random-effects meta-analysis was performed. In total, 24 studies (22 studies on paraoxonase and 11 on arylesterase activity) were eligibly identified. Patients with CKD showed a lower activity of paraoxonase (standard mean difference [SMD], −1.72; 95% confidence interval [CI], −2.15 to −1.29) and arylesterase (SMD, −2.60; 95%CI, −3.96 to −1.24) than healthy controls. In the subgroup analyses, paraoxonase activity was lower in chronic kidney failure (CKF), an advanced stage of CKD, than in non-CKF. In summary, PON1 activity is low in patients with CKD, suggesting that the antioxidant defense by PON1 is impaired in CKD. The decrease in enzyme activity is pronounced in advanced CKD showing some variability depending on the substrate employed to measure PON1 activity. Further studies are warranted.

Paraoxonase 1 Activity and Renal Replacement Therapy for Chronic Renal Failure: A Meta-Analysis

“…The network meta-analysis of arylesterase activity was performed in 22 studies. Healthy controls had higher activity relative to CRF patients in agreement with the previous report [7]. Arylesterase activity was significantly higher in CRF patients with RTx (SMD 1.84; 95% CI, 0.18-3.50) compared to those without RRT.…”

“…Given the importance of PON1 for CVD in CRF patients with RRT, the present comprehensive meta-analysis of studies was carried out to assess the effect of various RRT types on PON1 activity [2,4,6]. The analysis corroborated the earlier finding that healthy controls have higher PON1 activities than CFK patients [7]. Importantly, we observed that paraoxonase and arylesterase activities were highest in CRF patients receiving RTx, followed by higher activity levels in patients under HD and PD as compared to those not receiving RRT.…”

“…Our previous meta-analysis revealed that CRF patients without RRT had lower PON1 activity (arylesterase and paraoxonase) compared to healthy individuals, indicating PON1 may serve as a biomarker in CRF in relation to CVD [7]. However, an analysis of the current literature on the effects of RRT on PON1 activity in CRF patients remains needed.…”

Integrated metabolomics and proteomics reveal biomarkers associated with hemodialysis in end-stage kidney disease

“…Importantly, the serum protein–metabolite interactions that annotated in our integrated analysis revealed a larger network encompassing other components associated with clinical complications of ESKD. For instance, meta-analysis revealed that serum paraoxonase 1 (PON1) activity is likely reduced in CKD (decreased level shown in Figure 5C ), suggesting the antioxidant defense is impaired ( Watanabe et al, 2023 ). The beneficial role of PON1 activity on reducing the cardiovascular event has been reported ( Shih and Lusis, 2009 ).…”

Vitamin C supplementation and paraoxonase 1 activity in patients on hemodialysis: a meta-analysis

“…A high-density lipoprotein (HDL)-associated esterase called paraoxonase 1 (PON1), which is also known as arylesterase and paraoxonase (depending on the substrate employed in its measurement), inhibits the buildup of lipid peroxide on low-density lipoprotein, and low PON1 activity can raise the risk of cardiovascular events [ 5 , 6 ]. In addition, PON1 has been proposed as an antioxidant biomarker for monitoring CKD [ 7 ].…”