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

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.