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Association of Redox Status and Inflammatory Markers with Clinical Outcomes in Haemodialysis Patients
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Association of Redox Status and Inflammatory Markers with Clinical Outcomes in Haemodialysis Patients
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Department for Medical Biochemistry, Faculty of Pharmacy, University of Belgrade , Belgrade , Serbia
Department for Medical Biochemistry, Faculty of Pharmacy, University of Belgrade , Belgrade , Serbia
Department for Medical Biochemistry, Faculty of Pharmacy, University of Belgrade , Belgrade , Serbia
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Department of Hematology and Cytological Diagnostics of Fluids, Laboratory Diagnostics Service, Kliničko Bolnički Centar Zvezdara , Belgrade , Serbia
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Department of Hematology and Cytological Diagnostics of Fluids, Laboratory Diagnostics Service, Kliničko Bolnički Centar Zvezdara , Belgrade , Serbia
Department of Nephrology and Hemodialysis, Kliničko Bolnički Centar Zvezdara , Belgrade , Serbia
Faculty of Medicine, University of Belgrade , Belgrade , Serbia
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Department for Medical Biochemistry, Faculty of Pharmacy, University of Belgrade , Belgrade , Serbia
Department for Medical Biochemistry, Faculty of Pharmacy, University of Belgrade , Belgrade , Serbia
Editor: Bato Korac
Abstract
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.
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Funding Statement
The study was planned and conducted in accordance with applicable national regulations and the ethical principles of the Declaration of Helsinki, with prior approval from the Ethics Committee of the Clinical Hospital Center Zvezdara. All participants provided informed consent to participate in the study.
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