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Peroxisome proliferator-activated receptor-γ–coactivator 1α (PGC-1α) gene expression in chronic kidney disease patients on hemodialysis: relation to hemodialysis-related cardiovascular morbidity and mortality

  • Nephrology – Original Paper
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Abstract

Purpose

The aim of the current study was to investigate some of the key regulators of mitochondrial oxidative metabolism in ESRD patients on hemodialysis (ESRD/HD) focusing on peroxisome proliferator-activated receptor-γ–coactivator 1α (PGC-1α) gene expression and its relation to ESRD/HD-related cardiovascular diseases (CVD) and mortality in an effort to identify new potential targets for pharmacological interventions.

Subjects and methods

The expression of PGC-1α and one of its downstream genes: COX6C were evaluated in 49 ESRD/HD patients and in 33 age- and sex-matched healthy subjects as controls using quantitative real-time PCR. Malondialdehyde (MDA) was measured using colorimetric method as a marker of oxidative stress. Patients were followed up for 24 months for the development of HD-related cardiovascular complications and mortality.

Results

PGC-1α and COX6C expressions were significantly down-regulated in ESRD/HD patients compared to the controls (P ≤ 0.001 for both). Additionally, MDA level was higher in HD patients (P ≤ 0.001). Negative correlation was found between PGC-1α expression and MDA level (P ≤ 0.001). MDA was significantly higher, while PGC-1α expression was significantly lower in HD patients who developed CVD than in patients who did not. By using multivariate logistic regression analysis, it was found that down-regulated PGC-1α expression is independently associated with the development of CVD in HD patients.

Conclusion

Our study suggests that ESRD/HD patients might have oxidative mitochondrial dysfunction, which may be partially responsible for CKD-related cardiovascular complications. Pharmacological modulation of PGC-1α might be a promising therapeutic tool to reduce oxidative stress-related complications in ESRD/HD patients.

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Author information

Authors and Affiliations

  1. Clinical Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt

    Eman Tayae Elsayed

  2. Medical Biochemistry Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt

    Rasha Adel Nassra

  3. Internal Medicine Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt

    Yasmine Salah Naga

Authors
  1. Eman Tayae Elsayed
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  2. Rasha Adel Nassra
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  3. Yasmine Salah Naga
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Correspondence to Eman Tayae Elsayed.

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Ethical standards

This research was conducted on human participants. The study was approved by the Ethics Committee of Alexandria University, Egypt.

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Informed consent was obtained from all individual participants included in the study.”

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Elsayed, E.T., Nassra, R.A. & Naga, Y.S. Peroxisome proliferator-activated receptor-γ–coactivator 1α (PGC-1α) gene expression in chronic kidney disease patients on hemodialysis: relation to hemodialysis-related cardiovascular morbidity and mortality. Int Urol Nephrol 49, 1835–1844 (2017). https://doi.org/10.1007/s11255-017-1628-5

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  • DOI: https://doi.org/10.1007/s11255-017-1628-5

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