Eicosapentaenoic acid supplementation alleviates pruritus, enhances skin moisture, and mitigates depression in maintenance hemodialysis patients.

Background: The objective of this study is to investigate the effects of oral supplementation with eicosapentaenoic acid (EPA) on circulating inflammatory factors, cardiometabolic parameters, skin moisturization, and the consequent symptoms of pruritus and depression in maintenance hemodialysis patients. Materials and methods: A total of 60 maintenance hemodialysis patients with severe pruritus symptoms completed this randomized, placebo-controlled study. Subjects of treatment group (n = 30) were instructed to consume 1000 mg fish oil (>900 mg EPA) and subjects of placebo group (n = 30) were instructed to consume 1000 mg soybean oil twice daily for 3 months. 5-D pruritus scoring, the Beck Depression Inventory (BDI) scale, skin moisture, serum creatinine, inflammatory factors, and cardiometabolic parameters were examined at baseline, and at the first, second, and third month post-supplementation. Results: A significantly decreased pruritus level was observed in the treatment group, whereas an opposite result was observed in the placebo group. Increased skin moisture levels on both the face and arms were observed in the treatment group, but not in the placebo group. Supplementation of EPA significantly decreased serum CRP and IL-6 levels. Significant decreases in total cholesterol (CHO), and triglycerides (TG) levels were observed; however, a decrease in high-density lipoprotein (HDL) level was observed in the treatment group. There was no change in plasma creatinine (CR) observed in both groups. A significantly decreased BDI score was observed, whereas the opposite result was observed in the placebo group. A correlational study showed that the severity of pruritus was significantly associated with skin moisture and serum CRP. The severity of pruritus was also positively correlated with the BDI score. Conclusion: Supplementation of EPA may provide multiple benefits including alleviating pruritus symptoms, addressing skin dryness, and mitigating depression in maintenance hemodialysis patients.

N-Acetylcysteine Alleviates the Progression of Chronic Kidney Disease: A Three-Year Cohort Study.

Background and Objectives: The prevalence of chronic kidney disease (CKD) is approximately 10% of the population in many countries. CKD progresses to end-stage renal disease (ESRD), resulting in adverse outcomes, prolonged hospitalization, and increased healthcare costs. Therefore, reducing CKD progression to ESRD is recognized as an important health issue. Materials and Methods: Data from the study participants with stage 3 to stage 5 CKD (n = 7668) were collected from the National Health Insurance (NHI) program in Taiwan (1 November 2014 to 31 December 2020). CKD patients who had ingested or not ingested N-acetylcysteine (NAC) for three years were divided into the study group (NAC users; n = 165) and the control group (NAC non-users; n = 165) to explore whether NAC use could alleviate CKD progression and reduce the risks associated with hemodialysis in CKD patients. Results: The levels of serum creatinine (SCr) and estimated globular filtration rate (eGFR) were nearly unchanged and/or slightly changed in NAC users, but the SCr levels were slightly increased, and the eGFR levels were significantly decreased in NAC non-users at the six-month interval during the three years. A statistical difference was observed between the two groups for both levels from 12 months to 36 months. The incidence rate of hemodialysis was significantly lower in NAC users than in non-NAC users (4.8% vs. 12.7%, Wald test = 5.947, p = 0.015, OR = 34.9). These results indicated that NAC use may improve renal function of CKD patients by modulating SCr and eGFR and, in turn, reducing the risk of hemodialysis. Conclusions: We investigated whether NAC could be used to reduce CKD progression to ESRD. For the three-year retrospective study, the incidence rate of hemodialysis was significantly lower in NAC users than in non-NAC users via modulating SCr and eGRF levels. NAC use might be a useful clinical approach for reducing CKD progression to ESRD.

Chewing Gum May Alleviate Degree of Thirst in Patients on Hemodialysis.

Background and Objectives: Fluid restriction commonly causes dry mouth in patients on hemodialysis (HD). The observed effects of chewing gum on the amount of saliva, interdialytic weight gain (IDWG), and degree of thirst in patients on HD have been inconsistent. We investigated whether chewing gum can modulate these three parameters in patients on HD. Materials and Methods: We used purposive sampling to enroll 37 patients on HD who were then randomly divided into the chewing gum group (n = 19) and the control (non-chewing gum) group (n = 18). The degree of thirst was assessed using a self-rated visual analog scale (VAS) and a summated xerostomia inventory (SXI), respectively. Results: The degree of thirst after dialysis was significantly lower in the chewing gum group than in the control group. The amount of saliva was higher in the chewing gum group than in the control group before dialysis, but the saliva amount was comparable between the groups after dialysis. Furthermore, the amount of saliva was not associated with IDWG in patients on HD before or after dialysis. Conclusions: Chewing gum may alleviate the feeling of thirst but may not affect the amount of saliva and IDWG in patients on HD. Therefore, we suggest that chewing gum may be a useful approach to improve dry mouth and thirst in patients on HD.

Omega-3 Fatty Acids Improve Chronic Kidney Disease-Associated Pruritus and Inflammation.

Background and Objectives: Chronic kidney disease-associated pruritus (CKD-aP) is a common symptom in hemodialysis patients. A frequent and intense itching sensation largely torments patients, impacts quality of life outcomes, and it has an independent association with mortality. The objective of this study is to investigate the effects of oral supplementation with omega-3 polyunsaturated fatty acid (omega-3 PUFA) on circulating interleukin-6 (IL-6), cardiometabolic parameters, skin moisturization, and the consequent symptoms of pruritus in hemodialysis patients. Materials and Methods: Volunteers on maintenance hemodialysis with very severe pruritus symptoms were enrolled in this prospective cohort study. Subjects were instructed to consume 1000 mg fish oil once daily for 3 months. Pruritus scoring, skin moisture, plasma IL-6, and cardiometabolic parameters were measured at baseline, and at the first, second, and third month post-supplementation with fish oil for assessment of the clinical significance. Results: A total of 27 patients who had a mean age of 67.33 ± 11.06 years and 3.98 ± 3.23 years on hemodialysis completed the study. Supplementation with omega-3 PUFA significantly decreased IL-6 levels (p < 0.001), but increased the levels of c-reactive protein (CRP) (p < 0.05). Evaluation of the cardiovascular risk showed significant (all p < 0.001) decreases in the total cholesterol (CHO), low-density lipoprotein (LDL), and triglycerides (TG) levels, and an increase in the high-density lipoprotein (HDL) level. A significant decrease in plasma creatinine (CR) was observed (p < 0.001), but the decrease was limited. Supplementation with omega-3 PUFA significantly improved (all p < 0.001) skin hydration on both the face and arms, as well as disease-related symptoms of pruritus. Conclusion: Omega-3 PUFA supplementation improved inflammation, renal function, cardiovascular parameters, dry skin conditions, and the consequent symptoms of pruritus in hemodialysis patients.

Altered Mineral Metabolism and Disequilibrium Between Calcification Promoters and Inhibitors in Chronic Hemodialysis Patients.

Patients undergoing long-term hemodialysis (HD) are known to have abnormal blood concentrations of antioxidant minerals; concurrent oxidative stress can contribute to increased vascular calcification. This study aims to evaluate the associations between circulating antioxidant minerals and clinical biomarkers of vascular calcification in HD patients. Blood biochemical parameters, antioxidant minerals (selenium (Se), zinc (Zn), copper (Cu), and magnesium (Mg)), and several promoters and inhibitors of calcification (matrix Gla protein (MGP), fibroblast growth factor-23 (FGF-23), matrix metalloproteinases (MMP-2 and -9), and tissue inhibitors of metalloproteinase (TIMP-1 and -2)) were determined in HD patients (n = 62) and age- and sex-matched healthy individuals (n = 30). Compared with healthy subjects, HD patients had significantly lower plasma concentrations of Se and Zn, increased Cu and Mg, and higher levels of oxidative stress and inflammatory markers (Cu/Zn ratios, malondialdehyde (MDA), advanced glycation end products (AGEs), and C-reactive protein (CRP)). We observed that HD patients had significantly lower concentrations of MGP and higher levels of FGF-23, MMP-2 and -9, TIMP-1 and -2, and MMP-2/TIMP-2 and MMP-9/TIMP-1 ratios. We also observed significant relationships between the concentrations of these minerals and calcification biomarkers in HD patients. These results suggest that changes in the homeostasis of antioxidant minerals (Se, Zn, Cu, and Mg) may contribute to the effects of oxidative stress and inflammatory status, thereby participating in the mechanism for accelerated vascular calcification in patients undergoing long-term HD.

Zinc supplementation alters plasma aluminum and selenium status of patients undergoing dialysis: a pilot study.

End stage renal disease patients undergoing long-term dialysis are at risk for abnormal concentrations of certain essential and non-essential trace metals and high oxidative stress. We evaluated the effects of zinc (Zn) supplementation on plasma aluminum (Al) and selenium (Se) concentrations and oxidative stress in chronic dialysis patients. Zn-deficient patients receiving continuous ambulatory peritoneal dialysis or hemodialysis were divided into two groups according to plasma Al concentrations (HA group, Al > 50 g/L; and MA group, Al > 30 to ≤ 50 g/L). All patients received daily oral Zn supplements for two months. Age- and gender-matched healthy individuals did not receive Zn supplement. Clinical variables were assessed before, at one month, and after the supplementation period. Compared with healthy subjects, patients had significantly lower baseline plasma Se concentrations and higher oxidative stress status. After two-month Zn treatment, these patients had higher plasma Zn and Se concentrations, reduced plasma Al concentrations and oxidative stress. Furthermore, increased plasma Zn concentrations were related to the concentrations of Al, Se, oxidative product malondialdehyde (MDA), and antioxidant enzyme superoxide dismutase activities. In conclusion, Zn supplementation ameliorates abnormally high plasma Al concentrations and oxidative stress and improves Se status in long-term dialysis patients.

Effects of zinc supplementation on plasma copper/zinc ratios, oxidative stress, and immunological status in hemodialysis patients.

BACKGROUND: Patients undergoing hemodialysis (HD) have low plasma levels of zinc (Zn), high plasma levels of copper (Cu), and exhibit increased oxidative stress, inflammation, and immune abnormalities. We evaluated the effects of Zn supplementation on abnormal plasma Cu/Zn ratios and clinical outcomes in HD patients. DESIGN AND METHODS: Patients on long-term HD with lower than normal plasma concentrations of Zn (< 80 mg/dL) were randomized to receive daily oral Zn supplements (n = 40) or no supplements (n = 25) for eight weeks. Age- and sex-matched healthy individuals served as a control group (n = 38). A number of clinical parameters were measured before and after the supplementation period. RESULTS: Compared with healthy subjects, patients had significantly elevated plasma Cu concentrations and Cu/Zn ratios, as well as higher levels of oxidative stress and pro-inflammatory cytokines. Patients who received Zn supplements for eight weeks had higher plasma concentrations of Zn and lower concentrations of Cu, along with reduced Cu/Zn ratios, oxidative stress status, and inflammatory responses compared to patients who did not receive Zn. Patients receiving Zn also showed significantly higher percentages of CD4 and CD19 lymphocytes, and elevated CD4/CD8 ratios. CONCLUSIONS: Zn supplementation ameliorates abnormally high plasma Cu/Zn ratios and may reduce oxidative stress, improve inflammatory status, and maintain immune function in patients undergoing long-term HD.

Plasma aluminum is a risk factor for oxidative stress and inflammation status in hemodialysis patients.

OBJECTIVES: The association between aluminum (Al), essential trace metals, oxidative stress, and inflammation status was evaluated in hemodialysis patients. DESIGN AND METHODS: Biochemical parameters in blood were determined in long-term hemodialysis patients (n=69) and age- and sex-matched healthy individuals (n=30). RESULTS: Compared with healthy subjects, patients had significantly higher concentrations of plasma Al. Elevated Al was negatively associated with the essential metals zinc, selenium, and iron. Al concentrations were strongly and positively correlated with contents of the oxidation products malondialdehyde and protein carbonyl. Inverse relationships were observed between Al concentrations and reduced concentrations of glutathione, ß-carotene, vitamin C, and vitamin E. Patients were also observed to have significantly increased production values of plasma high-sensitivity C-reactive protein, tumor necrosis factor-α, and interleukin-5. CONCLUSION: An increased plasma Al concentration is associated with disturbed concentrations of essential metals, increased oxidative stress, and increased inflammation status in hemodialysis patients.

Cu/Zn ratios are associated with nutritional status, oxidative stress, inflammation, and immune abnormalities in patients on peritoneal dialysis.

OBJECTIVES: We evaluated the relationship of the plasma copper/zinc (Cu/Zn) ratio with nutritional status, inflammation, oxidative stress, and immune function in peritoneal dialysis patients. DESIGN AND METHODS: Clinical and laboratory parameters were measured in patients (n=45) and age- and sex-matched healthy individuals (n=30). RESULTS: There were significant negative correlations of the Cu/Zn ratio with nutrition-related parameters (body mass index [BMI], creatinine, hemoglobin, and albumin) and antioxidant (vitamin C and E) levels and positive correlations of the Cu/Zn ratio with the levels of high sensitivity C-reactive protein (hs-CRP) and oxidation products (malondialdehyde [MDA] and protein carbonyl). The Cu/Zn ratio was negatively correlated with the percentages of B- and T-lymphocyte subsets and the ratio of CD4/CD8 antigens. CONCLUSIONS: In peritoneal dialysis patients, elevated Cu/Zn ratios are associated with malnutrition, increased oxidative stress, inflammation, and disrupted immune status.

Linkage of some trace elements, peripheral blood lymphocytes, inflammation, and oxidative stress in patients undergoing either hemodialysis or peritoneal dialysis.

BACKGROUND: Changes in essential trace elements may affect the inflammatory and immunological state of patients on hemodialysis (HD) or peritoneal dialysis (PD). Therefore, we aimed to determine trace element content and markers of oxidative stress, inflammation, and immune status in HD and PD patients and to assess the relationships among these parameters. METHODS: Patients on either HD (n = 20) or PD (n = 20) and age-, sex-, body mass index-matched healthy individuals (n = 20) were enrolled in the study. The trace elements zinc, copper, selenium, and iron; markers of oxidative stress thiobarbituric acid reactive substances (TBARS) and protein carbonyl levels; activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase; percentages of CD3 T lymphocytes and the subsets CD4 and CD8; the CD4/CD8 ratio; and C-reactive protein (CRP) were measured. RESULTS: All dialysis patients had low levels of albumin and hemoglobin. Significantly decreased percentages of CD3 and CD4 T lymphocytes and increased levels of CRP, TBARS, and carbonyl compounds were observed in HD patients. HD patients also had elevated erythrocyte SOD, lower GPx and catalase activities, and decreased levels of Se, Zn, and Fe in comparison to PD patients and healthy subjects. In addition, CRP was positively associated with TBARS and carbonyl levels, but was significantly inversely associated with Zn and Se levels. Positive correlations were found between T lymphocyte CD3 and CD4 percentages and Zn, Se, and Fe levels. CONCLUSIONS: There were significant decreases in T lymphocyte-related immunological regulation and increased inflammation and oxidative stress in dialysis patients. Essential trace element status was independently related to immune status, inflammation, and oxidative damage.

Alterations in trace elements and oxidative stress in uremic patients with dementia.

The present study was conducted to compare the trace elements and oxidative status between uremic patients with and without dementia. Chronic hemodialysis patients with dementia (n = 20) and without dementia (n = 25), and age-matched healthy volunteers (n = 20) were enrolled. The nutritional status, blood levels of trace elements aluminum (Al), zinc (Zn), copper (Cu), magnesium (Mg) and iron (Fe), malondialdehyde (MDA), and protein carbonyl production, antioxidant enzymes glutathione peroxidase (GPx), and glutathione reductase (GR) activities were measured. No significant difference in nutritional status or clinical characteristics was observed between nondementia and dementia patients. However, uremic patients with dementia have significantly higher Al, Cu, and Mg and lower Zn concentrations, as well as increased Cu/Zn ratio in comparison to nondementia patients. There were statistically significant increased MDA and carbonyl production and decreased GPx and GR activities in dementia patients. Furthermore, the significant associations of Al, Mg, and Cu/Zn ratio with oxidative status in patients with dementia were noted. The dementia may initially worsen with abnormal metabolism of trace elements and oxidative stress occurrence. Our results suggest that abnormalities in trace element levels are associated with oxidative stress and may be a major risk factor in the dementia development of uremic patients.

Short- and long-term renal outcomes of immediate prophylactic hemodialysis after cardiovascular catheterizations in patients with severe renal insufficiency.

BACKGROUND: The short- and long-term effects of prophylactic hemodialysis (HD) immediately after cardiovascular catheterizations on renal function in patients with severe baseline renal insufficiency remain unknown though previous studies reported non-beneficial very-short-term effect in less severe patients. METHODS AND RESULTS: Patients who had pre-procedural serum creatinine (Scr) between 2.5 and 5.5 mg/dl were retrospectively studied. Twenty of them (14 M/6 F, aged 69 +/- 2 years) had received prophylactic HD after radiocontrast exposure and constituted the HD group. Another 20 patients were case-matched to the baseline demographics of the HD group and served as the non-HD group. The baseline Scr were 3.9 +/- 0.2 and 3.5 +/-0.2 mg/dl, respectively (p = NS). Although the Scr at 3 months was significantly higher in the HD group (4.3 +/- 0.3 vs. 3.4 +/- 0.2 mg/dl, p = 0.02), the absolute and percentage increments from baseline to 3 months (0.4 +/- 0.2 vs. 0.0 +/- 0.2 mg/dl, p = NS, and 11 +/- 5% vs. 1 +/- 7%, p = NS, respectively) and 6 months (0.6 +/- 0.3 vs. 0.4 +/- 0.4 mg/dl, p = NS, and 18 +/- 8% vs. 8 +/- 10%, p = NS, respectively) were not statistically different. Patients who developed end-stage renal disease requiring permanent HD at 1 year were also similar in both groups (four vs. three, respectively, p = NS). CONCLUSIONS: Our study confirmed that prophylactic HD immediately after contrast media administration in catheterizations failed to affect the short- and long-term renal and clinical outcomes even in patients with severe baseline renal insufficiency.

Association of JC virus with tubulointerstitial nephritis in a renal allograft recipient.

A renal allograft transplant patient with tubulointerstitial nephritis was examined for possible involvement of human polyomaviruses. Biopsy of the allograft kidney revealed inflammatory interstitial infiltration with tubulitis and typical inclusion bodies in the nucleus of the tubulo-epithelium. Glomeruli showed duplication and lamination of Bowman's capsule with enlargement of the parietal and visceral epithelia. Immunohistochemical analysis on the graft section using a JC virus (JCV) VP1 peptide-specific antibody showed positive staining. Paracrystalline arrays of naked viral particles with diameters of 40 nm were visualized in the nuclear inclusions under an electron microscope. Molecular examination using the polymerase chain reaction (PCR) and DNA sequencing revealed that the JCV was involved in the nephritis. The results indicated that JCV may be associated with tubulointerstitial nephritis.

Increased QTc dispersion and mortality in uremic patients with acute myocardial infarction.

QT dispersion (the difference between maximum and minimum QT across the 12-lead electrocardiogram [ECG]), which reflects regional variations in ventricular repolarization, is a predictor of arrhythmia and cardiovascular mortality. The present study was undertaken to assess the difference in QT dispersion between uremic and nonuremic patients with acute myocardial infarction (AMI) and its relationship to post-AMI clinical outcome. Twelve-lead ECG recordings were obtained the first and third days after the onset of AMI in 21 uremic and 21 nonuremic patients. QT intervals were measured on 12-lead ECGs and corrected by heart rate (QTc). Our findings show that uremic patients with AMI had greater QTc dispersion (84 +/- 35 versus 55 +/- 15 milliseconds; P < 0.001), a greater 1-year mortality rate (48% versus 18%; P = 0.003), and underwent fewer reperfusion therapies (5 of 21 versus 17 of 21 patients; P = 0.002) compared with nonuremic patients with AMI. Patients with AMI who died had greater QTc dispersion than those who survived (102 +/- 40 versus 67 +/- 40 milliseconds; P = 0.015). An optimal QTc dispersion cutoff value of 60 milliseconds had a sensitivity of 100% and specificity of 55% in predicting 1-year mortality in uremic patients with AMI. Uremic patients with AMI administered thrombolytic therapies (n = 5) had reduced 1-year mortality rates (0% versus 63%; P = 0.003) and shortened QTc dispersion from days 1 to 3 (changes in QTc dispersion between days 1 and 3, 29% +/- 9% decrease versus 13% +/- 5% increase; P = 0.001) compared with those without therapies (n = 16). Our findings suggest that greater QT dispersion is associated with greater total mortality, and thrombolytic therapies could reduce QTc dispersion and mortality in uremic patients with AMI. It is prudent to refine our current management regimen for uremic patients with AMI to improve the poor clinical outcome.