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Effect of febuxostat on oxidative stress in hemodialysis patients with endothelial dysfunction: a randomized, placebo-controlled, double-blinded study

  • Nephrology - Original Paper
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Abstract

Purpose

Oxidative stress, which is most likely a key mediator in the development of cardiovascular disease, is implicated in the progression and deterioration of chronic kidney disease. Patients on hemodialysis exhibit the excessive generation of oxidative stressors, which may also be responsible for the endothelial dysfunction prevalent in these patients. Febuxostat, an inhibitor of xanthine oxidase enzyme, is emerging as a novel drug in the amelioration of oxidative stress status. However, studies regarding its effect among hemodialysis patients are still lacking.

Methods

This prospective, block-randomized, double-blinded, placebo-controlled study was carried out to assess the effect of oral 40 mg febuxostat on oxidative stress in hemodialysis patients. In total, fifty-seven eligible patients were randomly assigned to either a drug group or a placebo group for the 2-month study period. Serum malondialdehyde (MDA) and serum superoxide dismutase (SOD) were assessed at baseline and at the end of the study. A correlation analysis between previously reported serum asymmetric dimethylarginine (ADMA), serum MDA and serum SOD was performed.

Results

Febuxostat significantly decreased the serum MDA and significantly increased the serum SOD, while no significant results were observed in the placebo group. A highly positive correlation between the MDA levels and ADMA levels at baseline was noticed in both groups, while there was a highly negative correlation between the SOD levels and ADMA levels at baseline in both groups. A positive correlation between the change in ADMA levels and MDA levels from baseline was observed only in the drug group.

Conclusion

Febuxostat appears to have a direct ameliorating effect on oxidative stress in hemodialysis patients with endothelial dysfunction.

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Funding

The research did not receive any specific grant from funding agencies in the public or commercial sectors.

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Authors and Affiliations

  1. Department of Clinical Pharmacy, Faculty of Pharmacy, Ain Shams University, Monazamet El-Wehda El-Afriqeya St., Abbassia, Cairo, Egypt

    Mona Alshahawey, Sara M. Shaheen & Nagwa Ali Sabri

  2. Department of Nephrology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

    Tamer Elsaid

Authors
  1. Mona Alshahawey
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  2. Sara M. Shaheen
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  3. Tamer Elsaid
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  4. Nagwa Ali Sabri
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Correspondence to Sara M. Shaheen.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Ethical committee of Faculty of Pharmacy, A.S.U.) and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Alshahawey, M., Shaheen, S.M., Elsaid, T. et al. Effect of febuxostat on oxidative stress in hemodialysis patients with endothelial dysfunction: a randomized, placebo-controlled, double-blinded study. Int Urol Nephrol 51, 1649–1657 (2019). https://doi.org/10.1007/s11255-019-02243-w

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  • DOI: https://doi.org/10.1007/s11255-019-02243-w

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