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The influence of Klotho protein and prooxidant–antioxidant balance combination on the mortality of HD patients

  • Nephrology - Original Paper
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Abstract

Purpose

End-stage renal disease patients on chronic hemodialysis (HD) have a shortened life expectancy compared to the general population. The aim of this study was to evaluate a possible link between three new and emerging factors in renal pathophysiology: Klotho protein, telomere length in peripheral blood mononuclear cells (TL) and redox status parameters before HD (bHD) and after HD (aHD), and to test mortality prediction capability of these emerging parameters in a population of HD patients.

Methods

The study included 130 adult patients with average age 66 (54–72), on HD (3 times per week; 4–5 h per session). Klotho level, TL, routine laboratory parameters, dialysis adequacy and redox status parameters: advanced oxidation protein products (AOPP), prooxidant–antioxidant balance (PAB), superoxide anion (O2.−), malondialdehyde (MDA), ischemia-modified albumin (IMA), total sulfhydryl group content (SHG), and superoxide dismutase (SOD) were determined.

Results

Klotho concentration was significantly higher aHD; 68.2 (22.6–152.9) vs. bHD 64.2 (25.5–119.8) (p = 0.027). The observed increase in TL was not statistically significant. AOPP, PAB, SHG, and SOD activity were significantly increased aHD (p > 0.001). The patients with the highest mortality risk score (MRS) had significantly higher PAB bHD (p = 0.002). Significantly lower O2.− (p < 0.001), SHG content (p = 0.072), and IMA (p = 0.002) aHD were found in patients with the lowest MRS values. Principal component analysis revealed redox balance-Klotho factor as a significant predictor of high mortality risk (p = 0.014).

Conclusion

Decreased Klotho and TL attrition as well as redox status disturbance could be connected with higher mortality rate in HD patients.

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Data availability

The data supporting this study’s findings are available from the corresponding author upon reasonable request.

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Acknowledgements

We are grateful to Dr. David R. Jones for his excellent help in English language correction of the manuscript.

Funding

From the Ministry of Education, Science and Technological Development, Republic of Serbia through Grant Agreement with University of Belgrade—Faculty of Pharmacy No: 451-03-47/2023-01/ 200161. The funding organization played no role in study design, in collection, in analysis and in interpretation of data in the writing the report nor in the decision to submit the report for publication.

Author information

Authors and Affiliations

  1. Laboratory Diagnostics Service, Zvezdara Clinical Hospital Center, Belgrade, Serbia

    Tamara Milošević

  2. Faculty of Pharmacy, Department for Medical Biochemistry, University of Belgrade, Belgrade, Serbia

    Tamara Milošević, Miron Sopić, Jelena Vekić, Azra Guzonjić, Sanja Vujčić, Milica Miljković-Trailović & Jelena Kotur-Stevuljević

  3. Clinical Department of Nephrology and Metabolic Disorders With Dialysis “Prof. Dr. Vasilije Jovanovic”, Zvezdara Clinical Hospital Center, Belgrade, Serbia

    Snežana Pešić & Radomir Naumović

  4. Faculty of Medicine, University of Belgrade, Belgrade, Serbia

    Radomir Naumović

  5. Department of Hematology and Cytological Diagnostics of Fluids Laboratory Diagnostics Service Zvezdara Clinical Hospital Center, Dimitrija Tucovica 161, 11120, Belgrade, Serbia

    Tamara Milošević

Authors
  1. Tamara Milošević
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All authors have accepted responsibility for the entire content of this manuscript and approved its submission. All authors contributed to: (1) substantial contributions to conception and design, or acquisition of data, or analysis and interpretation of data, (2) drafting the article or revising it critically for important intellectual content, and (3) final approval of the version to be published.

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Correspondence to Tamara Milošević.

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The authors declare that they have no conflict of interest.

Ethical approval

This study has complied with all the relevant national regulations, institutional policies and that listed in the Helsinki Declaration of Ethical Principles for Medical Research. The study was approved by the Ethic Committee of “Zvezdara” University Clinical Hospital Center on 22.01.2021.

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Informed consent was obtained from all individuals included in this study.

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Milošević, T., Sopić, M., Vekić, J. et al. The influence of Klotho protein and prooxidant–antioxidant balance combination on the mortality of HD patients. Int Urol Nephrol 56, 615–623 (2024). https://doi.org/10.1007/s11255-023-03696-w

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