Lack of association between mutations of gene-encoding mitochondrial D310 (displacement loop) mononucleotide repeat and oxidative stress in chronic dialysis patients in Taiwan.

BACKGROUND: Mitochondria (mt) are highly susceptible to reactive oxygen species (ROS). In this study, we investigated the association between a region within the displacement loop (D-loop) in mtDNA that is highly susceptible to ROS and oxidative stress markers in chronic dialysis patients. We enrolled 184 chronic dialysis patients and 213 age-matched healthy subjects for comparison. Blood levels of oxidative stress markers, such as thiobarbituric acid reactive substances (TBARS) and free thiol, and the mtDNA copy number were determined. A mononucleotide repeat sequence (CCCC...CCCTCCCCCC) between nucleotides 303 and 316-318 (D310) was identified in mtDNA. RESULTS: Depending on alterations in the D310 mononucleotide repeat, subjects were categorized into 4 subgroups: 7-C, 8-C, 9 or 10-C, and T-to-C transition. Oxidative stress was higher in chronic dialysis patients, evidenced by higher levels of TBARS and mtDNA copy number, and a lower level of free thiol. The distribution of 7-C, 8-C, and 9-10C in dialysis and control subjects was as follows: 7-C (38% vs. 31.5%), 8-C (35.3% vs. 43.2%), and 9-10C (24.5% vs. 22.1%). Although there were significant differences in levels of TBARS, free thiol, and the mtDNA copy number in the D310 repeat subgroups (except T-to-C transition) between dialysis patients and control subjects, post hoc analyses within the same study cohort revealed no significant differences. CONCLUSION: Although oxidative stress was elevated in chronic dialysis patients and resulted in a compensatory increase in the mtDNA copy number, homopolymeric C repeats in the mtDNA region (D310), susceptible to ROS, were not associated with oxidative stress markers in these patients.

Association between C-reactive protein and biomarkers of bone and mineral metabolism in chronic hemodialysis patients: a cross-sectional study.

OBJECTIVE: Both chronic inflammation and dysregulation of bone and mineral metabolism are closely related with long-term outcomes of dialysis patients. Our objective was to investigate the relationship between these two abnormalities. DESIGN: This was a cross-sectional study. SETTING: This study was performed at a hospital-based hemodialysis center. PATIENTS: We enrolled 448 (male, 198; female, 250) clinically stable hemodialysis patients. Patients with chronic inflammatory disease, malignancy, or viral hepatitis were excluded. Their age (mean +/- SD) was 57.4 +/- 12.5 years. MAIN OUTCOME MEASURES: Biomarkers, including high-sensitivity C-reactive protein (hsCRP), total calcium, phosphate, and intact parathyroid hormone levels, were measured and compared with the recommended range in the K/DOQI guidelines. Correlations between these parameters were analyzed, and factors independently associated with hsCRP and the calcium phosphate product (Ca x P) were identified by regression analysis. RESULTS: Most patients did not achieve the K/DOQI recommended therapeutic range in the four parameters, and only 50 patients (11%) met their treatment goals. The hsCRP level was directly related to calcium, phosphate, and Ca x P. Patients who achieved the guidelines' range had lower hsCRP levels (1.97 mg/L vs. 2.71 mg/L, P < .05). A high hsCRP level (> or = 10 mg/L) was associated with higher calcium, phosphate, and Ca x P levels, and lower albumin levels. Serum albumin, Ca x P, alkaline phosphatase, and diabetes independently predicted hsCRP levels. CONCLUSION: There is a strong association between chronic inflammation and the disturbance of bone mineral metabolism in chronic hemodialysis patients.

Successful treatment of bilateral emphysematous pyelonephritis in a uremic patient without nephrectomy.

Emphysematous pyelonephritis (EPN) is a severe and complicated renal infection characterized by gas formation within the infected kidney and its surrounding tissues. Early diagnosis with a high index of suspicion and aggressive treatment are important for improving outcome. Bilateral involvement is rare, and surgical intervention is usually required because of its high mortality rate. A literature review found that EPN has rarely been noted in chronic dialysis patients, and those who show bilateral EPN have demonstrated no survival at all until now. Herein, we presented a 51-year-old diabetic uremic woman who developed right emphysematous pyelitis initially and then progressed to bilateral EPN when hospitalized. Percutaneous drainage (PCD) with simultaneous antibiotic therapy successfully eradicated her renal infection. In this study, all reported cases of EPN in chronic dialysis patients were also reviewed.

Correlation of oxidative stress biomarkers and peritoneal urea clearance with mitochondrial DNA copy number in continuous ambulatory peritoneal dialysis patients.

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, R(2) = 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.

Better sleep quality and less daytime symptoms in patients on evening hemodialysis: a questionnaire-based study.

The aims of this study were to investigate the prevalence of sleep disorders in patients with end-stage renal disease (ESRD), and to assess the effect of dialysis schedule on sleep quality and the presence of daytime symptoms. We prospectively selected 150 long-term hemodialysis (HD) patients in three groups (morning, afternoon, and evening dialysis) and gave them a sleep questionnaire, the Epworth sleepiness scale and the Pittsburgh sleep quality index. Snoring was the most common complaint (56%), followed by insomnia (38%) and restless legs syndrome (22.7%). The evening dialysis group experienced more sleep time in bed (P = 0.02), required less hypnotic medication (P = 0.049), had fewer daytime symptoms (P < 0.01), and experienced less daytime sleepiness (P = 0.034). Our study confirms the high prevalence of sleep disorders in ESRD patients, and indicates a beneficial effect of evening HD on sleep quality and reduction of daytime symptoms.

Mitochondrial DNA copy number correlates with oxidative stress and predicts mortality in nondiabetic hemodialysis patients.

BACKGROUND: Oxidative stress is highly prevalent in hemodialysis patients and may contribute to atherosclerosis and mortality. The copy number of mitochondrial DNA (mtDNA) is affected by oxidative stress in blood circulation. This study aimed to test whether mtDNA copy number correlates with oxidative stress and predicts all-cause mortality in nondiabetic hemodialysis patients. METHODS: Ninety-five nondiabetic hemodialysis patients and 95 healthy subjects were enrolled. Plasma thiobarbituric acid-reactive substances (TBARS) and plasma free thiol were used as indicators of oxidative stress and antioxidant defense, respectively. Mitochondrial DNA copy number in peripheral blood leukocytes was measured by determining relative amounts of mtDNA to nuclear DNA by quantitative real-time PCR. All-cause mortality of hemodialysis patient was recorded during a follow-up of 3 years. RESULTS: Nondiabetic hemodialysis patients showed higher TBARS levels, lower free thiol levels and higher mtDNA copy numbers compared with normal control subjects. The plasma TBARS level was a significant factor correlating positively to the mtDNA copy number (p=0.024). Patients with a mtDNA copy number higher than the median had a higher all-cause mortality than patients with a lower mtDNA copy number (17.0% vs. 4.2%; log-rank test: p=0.038). A 1-log increase in mtDNA copy number was independently related to an increase in the risk for mortality (hazard ratio 21.360; 95% confidence interval, 1.298-351.572). CONCLUSIONS: Nondiabetic hemodialysis patients had higher oxidative stress and mtDNA copy numbers than healthy subjects. The mtDNA copy number correlates with oxidative stress and predicts mortality in nondiabetic hemodialysis patients.