Purpose: This study aimed to investigate the association between paraoxonase 1 (PON1) activity phenotypes and redox status parameters, while evaluating the role of the pro-inflammatory cytokine tumor necrosis factor-alpha (TNF-α) as a predictor of mortality and cardiovascular risk in patients undergoing chronic haemodialysis (HD).
Methods: This study cohort comprised patients with end-stage renal disease (ESRD). PON1 paraoxonase (POase) and arylesterase (ARE) activities, alongside a comprehensive redox profile, were determined spectrophotometrically. TNF-α concentrations were quantified via ELISA. PON1 phenotypes (QQ, QR, RR) were assigned using the POase/ARE ratio and the antimodal method. Survival analysis was performed using the Kaplan-Meier method.
Results: The RR phenotype was the most prevalent among HD patients (43.2%) and was significantly associated with the highest levels of oxidative stress, specifically elevated total oxidative status (TOS) and advanced oxidation protein products (AOPP) (p < 0.001). TNF-α concentrations were significantly higher in patients who died during the study compared to survivors (5.22 vs. 3.45 pg/mL, p = 0.050). Kaplan-Meier analysis confirmed that TNF-α levels > 5 pg/mL are a significant predictor of shorter survival (log-rank = 4.21, p = 0.040). Elevated TNF-α directly correlated with dyslipidemia progression and a higher atherosclerosis index.
Conclusions: The PON1 RR phenotype and elevated TNF-α concentrations (> 5 pg/mL) serve as critical biomarkers of oxidative and inflammatory status in HD patients. Their synergistic interaction contributes to accelerated atherogenesis and increased mortality, highlighting their utility in clinical risk stratification.