Correlation of Oxidative Stress Biomarkers and Peritoneal Urea Clearance with Mitochondrial DNA Copy Number in Continuous Ambulatory Peritoneal Dialysis Patients

Abstract

Background/Aims: The influence of oxidative stress and peritoneal clearance on alterations in mitochondrial DNA (mtDNA) copy number in continuous ambulatory peritoneal dialysis (CAPD) patients was investigated. Methods: Ninety-one CAPD patients (age, 30–57 years) and 99 age-matched healthy subjects were enrolled. Biochemical variables, plasma thiobarbituric-acid-reactive substances (TBARS), free thiol levels and mtDNA copy number in peripheral leukocytes were measured. Results: CAPD patients showed higher TBARS levels, lower free thiol levels and a higher mtDNA copy number than control subjects. Plasma TBARS levels and peritoneal urea clearance were significant factors contributing positively to leukocyte mtDNA copy number (p = 0.024, R² = 0.238). The CAPD patients were further categorized into 4 groups depending on whether the TBARS and free thiol plasma levels were above or below the mean values for these parameters. Patients with higher TBARS levels and lower free thiol levels had a significantly higher number of leukocyte mtDNA copies than patients with lower TBARS levels and higher free thiol levels (multi-covariate ANOVA, p = 0.008). Conclusion: This study demonstrated that CAPD patients have higher oxidative stress than healthy subjects; such elevated oxidative stress and peritoneal urea clearance have a positive correlation with mtDNA copy number in peripheral leukocytes.

Sequence-Based Polymorphisms in the Mitochondrial D-Loop and Potential SNP Predictors for Chronic Dialysis

“…For example, elevated oxidative stress in chronic peritoneal dialysis patients may lead to alterations in the mtDNA copy number in peripheral leukocytes [33]. In our current study, the mtSNPs listed in Table 3 were homoplasmic, as revealed by sequencing chromatograms (data not shown) [58]–[60].…”

“…The acquisition of ROS-induced mutations in CKD may be a consequence of increased oxidative burden in patients with chronic renal failure [9], [32], [33], [57]. For example, elevated oxidative stress in chronic peritoneal dialysis patients may lead to alterations in the mtDNA copy number in peripheral leukocytes [33].…”

“…CKD patients can be classified according to kidney function along a continuum from mild renal dysfunction to irreversible kidney failure. CKD increases oxidative stress [32] which has been demonstrated to influence mtDNA content in CKD patients [33], [34].…”

Mitochondrial DNA alteration and pathological progression in colorectal cancer

“…While in chronic renal failure cases the increased mtDNA content was identified in white blood cell. Although this disease is accompanied with high oxidative stress too, the inflammation is also involved [48] . The similarly increased mtDNA content also showed in septic shock, while testing the blood of patients [49] .…”

Low Mitochondrial DNA Copy Number is Associated With Adverse Clinical Outcomes in Peritoneal Dialysis Patients

“…15,16 A low mtDNA copy number correlates with increased oxidative stress and higher mortality rates in patients undergoing dialysis. In a uremic rat model, the mtDNA copy number was also significantly decreased compared to control rats, and was associated with decreased renal function.…”