Is regular in-person recall superior to non-regular in-person recall in clinical outcomes among new patients undergoing peritoneal dialysis.

OBJECTIVE: To investigate the different impacts on clinical outcomes between regular recall and non-regular recall among incident peritoneal dialysis (PD) patients. METHODS: A two-center cohort of 216 new PD patients from 1January 2013, to 31 December 2014, was studied. Informative clinical data were collected from baseline until two years after PD initiation, including demographics, laboratory and PD-related parameters, PD-related peritonitis rates, and frequency of hospitalization. Regular in-person recall (RPR) was defined as having a one-month interval and non-regular in-person recall (NRPR) as an interval ranging from more than one month to less than three months. RESULTS: Percentage of patients with peritonitis was significantly higher among patients in the NRPR group than among those in the RPR group (27.7% vs. 16.5%, p = .049). PD-related peritonitis rate was higher in the NRPR vs. RPR cohorts (0.16 vs. 0.09 person/year, p = .019). PD-related hospitalization frequency was also higher in the NRPR cohort (0.8 ± 1.0 vs. 0.5 ± 0.9, p = .039) over two years. Kt/V values in the NRPR cohort gradually decreased over two years and were at lower levels than in the RPR cohort. CONCLUSIONS: New PD patients with NRPR showed higher rates of PD-related peritonitis and hospitalization frequency than patients with RPR.

Effect of clinical factors on trajectory of functional performance in patients undergoing hemodialysis.

PURPOSE: This study aimed to investigate the association between clinical factors and temporary changes in functional performance in patients undergoing hemodialysis. METHODS: This was a retrospective, longitudinal observational study conducted from 2015 to 2017. Eight-two patients undergoing hemodialysis in the outpatient clinic were enrolled. Functional performance was measured using the Karnofsky Performance Status (KPS) scale. Collected data for analysis included demographics, laboratory parameters, and KPS scale scores. All participants were grouped into a high KPS cluster and a low KPS cluster based on dynamic changes in KPS scales from 2015 to 2017. RESULTS: Participants in the high KPS cluster demonstrated an approximate trend, and those in the low KPS cluster demonstrated a low pattern. By stepwise selection model analysis, age (OR 1.12, 95% CI 1.03-1.23, p = 0.011), serum BUN (OR 1.08, 95% CI 1.02-1.16, p = 0.015), calcium levels (OR 3.24, 95% CI 1.2-8.73, p = 0.02), and beta-2-microglobulin (OR > 1.0, CI >1.00-<1.01, p = 0.031) showed risk for the low KPS cluster. Male sex (OR 0.20, 95% CI 0.04-0.96, p = 0.045) and albumin level (OR 0.02, 95% CI 0-0.4, p = 0.009) showed a low risk for the low KPS cluster. CONCLUSIONS: A different trajectory pattern was observed between the high and low KPS clusters in a 3-year period. Risk factors for the low KPS cluster were age, serum BUN, calcium, and beta-2-microglobulin levels. Male sex and serum albumin levels reduced the risk for the low KPS cluster.

Empagliflozin Ameliorates Free Fatty Acid Induced-Lipotoxicity in Renal Proximal Tubular Cells via the PPARγ/CD36 Pathway in Obese Mice.

High serum levels of free fatty acids (FFAs) could contribute to obesity-induced nephropathy. CD36, a class B scavenger receptor, is a major receptor mediating FFA uptake in renal proximal tubular cells. Empagliflozin, a new anti-diabetic agent, is a specific inhibitor of sodium-glucose co-transporter 2 channels presented on renal proximal tubular cells and inhibits glucose reabsorption. In addition, empagliflozin has shown renoprotective effects. However, the mechanism through which empagliflozin regulates CD36 expression and attenuates FFA-induced lipotoxicity remains unclear. Herein, we aimed to elucidate the crosstalk between empagliflozin and CD36 in FFA-induced renal injury. C57BL/6 mice fed a high-fat diet (HFD) and palmitic acid-treated HK-2 renal tubular cells were used for in vivo and in vitro assessments. Empagliflozin attenuated HFD-induced body weight gain, insulin resistance, and inflammation in mice. In HFD-fed mice, CD36 was upregulated in the tubular area of the kidney, whereas empagliflozin attenuated CD36 expression. Furthermore, empagliflozin downregulated the expression of peroxisome proliferator-activated receptor (PPAR)-γ. Treatment with a PPARγ inhibitor (GW9662) did not further decrease PPARγ expression, whereas a PPARγ antagonist reversed this effect; this suggested that empagliflozin may, at least partly, decrease CD36 by modulating PPARγ. In conclusion, empagliflozin can ameliorate FFA-induced renal tubular injury via the PPARγ/CD36 pathway.

Relationship between trajectory of sleep quality and short-term changes in residual renal function in stage 3-5 chronic kidney disease patients.

BACKGROUND: Chronic kidney disease (CKD) is commonly associated with sleep disturbance. However, the relationship between the trajectory of sleep quality and short-term residual renal function is not clear. Thus, this study aimed to investigate such relationship. METHODS: In total, 132 patients with CKD stage 3-5 were prospectively enrolled. All participants were followed-up for 6 months. The Pittsburgh Sleep Quality Index (PSQI) questionnaire was used to assess sleep quality. The longitudinal PSQI and estimated glomerular filtration rate (eGFR) were measured at baseline, the 3rd month and 6th month. The participants were stratified into three groups according to the PSQI trajectories. The primary outcome was set as the eGFR change among 6 months less than the median. RESULTS: Sixty nine participants showed PSQI ≤ 5 at baseline and 15 patients had increased scores > 5 at 3rd month among them. 63 participants showed PSQI > 5 at baseline and 11 patients had decreased scores ≤ 5 at 3rd month. Only in patients whose baseline PSQI ≤ 5 but increased to > 5 at 3rd month presented a longitudinal decline in eGFR at both 3rd month and 6th month compared with baseline eGFR. Linear regression analysis for eGFR change showed no significant association between eGFR change and PSQI score. Logistic regression revealed worsen sleep quality will deteriorate renal function. CONCLUSION: A relationship was observed between worsening sleep quality and eGFR decline in non-dialysis CKD patients.

Importance of non-medical reasons for dropout in patients on peritoneal dialysis.

BACKGROUND: To describe the associated factors for non-medical reasons for dropout in peritoneal dialysis (PD) patients. METHODS: A retrospective cohort study was performed using registry data of adult patients commencing PD as their initial renal replacement therapy in one hospital-facilitated PD center in Taiwan between 2014 and 2018. The collected data included socio-demographics and relevant medical and PD-related parameters. Kaplan-Meier analysis was used to determine the impact of non-medical reasons and medical reasons on PD dropout. RESULTS: The analysis included 224 PD patients, of whom 37 dropped out for non-medical reasons and 187 for medical reasons during the study period. There was significant difference between the two cohorts in age (62.3 years vs. 56.1 years, P = 0.010) and PD vintage (median 3.4 years vs. 4.8 years, P = 0.001). Diabetes was more predominant in the cohort for non-medical reasons than in the one for medical reasons (54.1% vs. 27.3% respectively, P = 0.001). In non-medical reason cohort, two leading reasons given for dropping out were lacking of caregivers (n = 12) and losing confidence (n = 10), whereas PD-related peritonitis (n = 101) was the main medical reason for PD dropout. Using Kaplan-Meier curve analysis, patients in the non-medical reason cohort demonstrated higher cumulative dropout rate compared to patients in the medical reason cohort during a 10-year period (P < 0.001). CONCLUSIONS: The main characteristics of PD dropout patients for non-medical reasons are age, diabetes, patients' perception and caregiver support.

Correlation of sociodemographic profiles with psychological problems among hospitalized patients receiving unplanned hemodialysis.

Purpose: In this prospective study, we aimed to examine the sociodemographic factors and clinical factors associated with psychological disorders in chronic kidney disease (CKD) patients receiving unplanned hemodialysis (HD).Methods: We prospectively enrolled 187 CKD stage 5 patients receiving unplanned HD at a tertiary hospital from January 2015 to December 2016. We used structured questionnaires to gather data about participants' anxiety, depression, and sleep disturbance. Generalized linear regression analysis was used to examine the relationships between sociodemographic and laboratory parameters, and severity of psychological distress.Results: The mean age of the participants was 60 years, and the number of men and women was 97 and 90, respectively. We did not find a significant association between anxiety, depression, and sleep disturbance scores and gender, age, marital status, religion status, education levels, and employment status and number of comorbidities. Generalized linear regression analysis showed that a multidisciplinary CKD care program in outpatient clinic disclosed a significant negative association with psychological disorders in participants.Conclusions: CKD patients exhibited psychological distress when receiving unplanned HD, not closely associated with sociodemographic profiles.

Comparison of Solute Clearance, Hospitalization Rate, and Aortic Arch Calcification between Online Hemodiafiltration and High-Flux Hemodialysis: A 6-Year Observational Study.

BACKGROUND/AIMS: Studies on the long-term clinical benefits of hemodiafiltration (HDF) and high-flux hemodialysis (HFHD) are very limited. This study aimed to investigate the hospitalization rate and aortic arch calcification (AAC) of these two dialysis modalities over 6 years. METHODS: Participants who received regular HDF and HFHD in one hospital-facilitated hemodialysis center were prospectively enrolled after matching for age, sex, and diabetes between January 2009 and December 2014. Medical records were reviewed retrospectively on demographics, laboratory variables, calcified scores in aortic arch measured by chest radiography, and rates of hospital admission. Cox proportional hazard regression and linear regression were used to obtain the outcome results. RESULTS: The HDF and HFHD groups consisted of 108 and 102 participants, respectively. Levels of laboratory variables including small soluble solutes and Kt/V were not statistically different over the 6-year period between the HDF and HFHD groups. Calcified scores of the aortic arch increased over 6 years in both groups. The changes in the mean calcified scores were significant when compared between the two groups (0.44-1.82 in HFHD, 0.79-1.8 in HDF, respectively, p = 0.008). Hospitalization rates were 735 per 1,000 patients in the HDF group and 852 per 1,000 patients in the HFHD group, respectively. No significant difference was observed in frequency and days of hospitalization between HDF and HFHD. CONCLUSION: Hospitalization rates and AAC were observed to be equal for HDF and HFHD.

Effects of Peritoneal Dialysis on Clinical Factors and Functional Performance.

BACKGROUND: We investigated the longitudinal trend of functional performance in peritoneal dialysis (PD) patients over 1 year after PD commencement and its related clinical parameters. METHODS: One hundred and ninety-six PD patients were enrolled in this study. Karnofsky Performance Status Scale(KPSS) scores were used to assess functional performance. Patients were stratified into 3 groups according to the changes in KPSS from baseline to 1 year. A logistic regression analysis was performed to examine the associations of clinical parameters with KPSS changes. RESULTS: Patients with KPSS declined showed older age and higher serum albumin concentration reduction within 1 year than those in KPSS improved and stable changes. Age was the significant risk factor for KPSS decline, while male and diabetes were significantly associated with non-declined KPSS by multivariable logistic regression analysis. CONCLUSION: The main determinants of KPSS trend were age, sex, and diabetes in new PD patients.

Time-varying serum albumin levels and all-cause mortality in prevalent peritoneal dialysis patients: a 5-year observational study.

BACKGROUND: In this study, we investigated the association of time-varying serum albumin levels with mortality over a 5-year period in one cohort of patients undergoing long-term peritoneal dialysis (PD) therapy. METHODS: The participants in this study enrolled 302 patients who underwent long-term PD at a single PD center in Taiwan. We reviewed medical records from 2011 to 2015 retrospectively. Time-averaged albumin level and serum albumin reach rate (defined as the percentage of serum albumin measurements that reached ≥3.5 g/dL) were applied as the predictor variables in the first 2 years (2011-2012). All-cause mortality was used as the outcome variable in the subsequent 3 years (2013-2015). Hazard function of all-cause mortality in the study participants was examined by using Cox proportional hazard regression models . RESULTS: Patients with different albumin reach rates (75-< 100%, 50-< 75%, 1-< 50%) did not exhibit a significantly increased risk for all-cause mortality. Patients with a 0% albumin reach rate exhibited a significantly increased risk for all-cause mortality (hazard ratio [HR] 7.59, 95% confidence interval [CI], 2.38-24.21) by fully adjusted analysis. Patients with time-averaged albumin levels of < 3.5 g/dL (HR 15.49, 95% CI 1.74-137.72) exhibited a higher risk for all-cause mortality than those with serum albumin levels ≥4.0 g/dL. CONCLUSIONS: This study demonstrated that higher serum albumin reach rates and higher time-averaged serum albumin levels are associated with a lower mortality rate over a 5-year period among patients undergoing long-term PD.

Comparison of tunneled central venous catheters and native arteriovenous fistulae by evaluating the mortality and morbidity of patients with prevalent hemodialysis.

PURPOSE: We examined the association between catheter use for maintenance hemodialysis (HD) and mortality/hospitalization in a cohort of patients with prevalent HD. METHODS: In this study, 70 HD patients with tunneled cuffed central venous catheters (TCVCs) from a Taiwanese HD center during 2014-2016 were enrolled and compared with 70 matched HD patients with native arteriovenous fistulae (AVF). The compared variables included demographic parameters and laboratory and dialysis-related indices. Cox regression analysis was used to assess the risk of mortality/hospitalization within a year. RESULTS: Low baseline serum albumin levels were found in patients with TCVCs (3.64 g/dL vs 3.79 g/dL, p = 0.030). The mortality rates of patients with AVF and TCVCs were 14 per 1000 patients and 171 per 1000 patients, respectively. Infection was the leading cause of mortality/hospitalization in patients with TCVCs. Using multivariate analyses, the risk of death was found to be significantly higher in patients with TCVCs than in those with AVF (Hazard ratio [HR] 12.15, 95% CI 1.16-127.17; p = 0.037). Patients with TCVC also had a higher hospitalization rate (HR 1.33, 95% CI 0.71-2.49; p = 0.369) (not statistically significant). CONCLUSION: Catheter use for maintenance HD was associated with increased all-cause mortality.

Palmitate aggravates proteinuria-induced cell death and inflammation via CD36-inflammasome axis in the proximal tubular cells of obese mice.

High levels of serum free fatty acids (FFAs) and proteinuria have been implicated in the pathogenesis of obesity-related nephropathy. CD36, a class B scavenger receptor, is highly expressed in the renal proximal tubules and mediates FFA uptake. It is not clear whether FFA- and proteinuria-mediated CD36 activation coordinates NLRP3 inflammasomes to induce renal tubular injury and inflammation. In this study, we investigated the roles of CD36 and NLRP3 inflammasomes in FFA-induced renal injury in high-fat diet (HFD)-induced obesity. HFD-fed C57BL/6 mice and palmitate-treated HK2 renal tubular cells were used as in vivo and in vitro models. Immunohistochemical staining showed that CD36, IL-1ß, and IL-18 levels increased progressively in the kidneys of HFD-fed mice. Sulfo- N-succinimidyl oleate (SSO), a CD36 inhibitor, attenuated the HFD-induced upregulation of NLRP3, IL-1ß, and IL-18 and suppressed the colocalization of NLRP3 and ASC in renal tubular cells. In vitro, SSO abolished the palmitate-induced activation of IL-1ß, IL-18, and caspase-1 in HK2 proximal tubular cells. Furthermore, treatment with SSO and the knockdown of caspase-1 expression by siRNA both inhibited palmitate-induced cell death and apoptosis in HK2 cells. Collectively, palmitate causes renal tubular inflammation, cell death, and apoptosis via the CD36/NLRP3/caspase-1 axis, which may explain, at least in part, the mechanism underlying FFA-related renal tubular injury. The blockade of CD36-induced cellular processes is therefore a promising strategy for treating obesity-related nephropathy.

Association between Extreme Values of Markers of Chronic Kidney Disease: Mineral and Bone Disorder and 5-Year Mortality among Prevalent Hemodialysis Patients.

BACKGROUND/AIMS: We examined the association between markers of chronic kidney disease - mineral and bone disorder (CKD-MBD) and mortality in hemodialysis (HD) patients. METHODS: We retrospectively reviewed the association between markers of CKD-MBD and mortality in 1,126 HD patients from 2009 to 2013 with baseline (B), time-average (TA), and time-dependent (TD) Cox regression models. RESULTS: Hypercalcemia (10.9-11.9 mg/dL) indicated an increased risk of all-cause mortality (TA: hazard ratio [HR] 3.49; p = 0.01). Hypophosphatemia (2.0-2.5 mg/dL) was significantly associated with an increased risk of all-cause mortality (TA: HR 5.18; p = 0.01). Hypophosphatemia (<2.0 mg/dL) was significantly associated with an increased risk of cardiovascular mortality in all models. Intact parathyroid hormone levels <60 and >1,500 pg/mL indicated an increased risk of all-cause mortality (TA: HR 1.64; p = 0.02; TD: HR 2.26; p = 0.02). CONCLUSION: Extreme values of CKD-MBD markers are associated with mortality risk in HD patients. Video Journal Club 'Cappuccino with Claudio Ronco' at http://www.karger.com/?doi=478972.

Factors Associated with Functional Performance among Patients on Hemodialysis in Taiwan.

BACKGROUND/AIMS: We investigated factors associated with functional performance in hemodialysis (HD) patients as well as their relationships with mortality. METHODS: We enrolled 790 HD patients who were followed up from 2009 to 2013. Functional performance was evaluated by Karnofsky Performance Status Scale (KPSS) scores. We examined the associations of clinical variables and all-cause mortality with KPSS scores. RESULTS: Of the participants, 460 had high KPSS scores (range 90-100) and 330 had low KPSS scores (below 80). On multivariate analysis, age and weekly HD sessions were associated with significantly increased odds of a lower KPSS score (age: OR 1.05, 95% CI 1.04-1.07, p < 0.001; weekly HD: OR 2.10, 95% CI 1.37-3.21, p = 0.001). A low KPSS score was a significant predictor of increased all-cause mortality (hazard ratio 1.49; 95% CI 1.02-2.16, p = 0.037), as determined using Cox regression analysis. CONCLUSION: Functional performance was associated with clinical variables and all-cause mortality in HD patients.

Viridans streptococcus peritonitis in peritoneal dialysis: clinical characteristics and comparison with concurrent polymicrobial infection.

BACKGROUND: The clinical course of Viridans streptococci (VS) peritonitis in patients undergoing peritoneal dialysis (PD) is rarely reported. This study examined the association of clinical factors with VS peritonitis. METHODS: We retrospectively reviewed clinical data from patients with VS peritonitis from March 1990 to February 2016 in a PD center in Taiwan and evaluated clinical profiles and treatment outcomes. RESULTS: A total of 109 episodes of VS peritonitis in 71 patients identified. Among these patients, 57 had mono-VS peritonitis and 14 had concurrent polymicrobial infections. The median time interval from PD initiation to the first VS peritonitis episode was 18 months (range, 0.6-144 months). Among clinical outcomes, most VS peritonitis episodes were completely cured regardless of a history of peritonitis. All episodes with catheter removal occurred in those without a history of recent antibiotic use. CONCLUSION: VS peritonitis in patients undergoing PD typically has favorable treatment outcomes. Antibiotic therapy should be started promptly.

Longitudinal analysis of cardiac structure and function in incident-automated peritoneal dialysis: comparison between icodextrin solution and glucose-based solution.

BACKGROUND: This study aimed to evaluate the longitudinal changes in cardiac structure and function in incident-automated peritoneal dialysis (APD) patients. METHODS: We conducted a 2-year prospective, randomized, open-label, parallel-group study to compare the efficacy of icodextrin solution versus glucose-based solution. Echocardiography was performed at baseline, 1 and 2 years. Echocardiographic parameters over 2 years were evaluated for each group, using the Friedman test. Generalized linear regression analysis was used to test the associations between baseline clinical variables and echocardiographic changes, and a multivariate model was used to analyze cardiac function between the two groups. RESULTS: A total of 43 APD patients were enrolled in the beginning of this study. Twenty patients in the icodextrin group (ICO) and 18 patients in the glucose group (GLU) completed the study. In left ventricular (LV) systolic function measurements, ejection fraction (EF) increased significantly in the GLU group. Measurements of LV diastolic function and septal early mitral annulus velocity (EMV) increased significantly from baseline to 24-months in the ICO group (5.43-5.51 ms). The GLU group showed a significant decrease in peak early diastolic velocity (EDV) (70.67-68.25 cm/s), but a significant increase in septal EMV (5.94-7.57 ms) from baseline to 24-months. No significant association was found between the baseline clinical variables and echocardiographic changes within 24 months in the generalized linear regression analysis. Multivariate models were used to investigate changes in the four primary endpoints, namely, myocardial performance index (MPI), left ventricular ejection fraction (LVEF), deceleration time (DT), and E/e' ratio. These primary endpoints show no significant association with the baseline values in both the ICO and GLU groups. CONCLUSION: The present study demonstrates that long-dwell icodextrin solution can maintain reasonable cardiac structure and function in incident-APD patients. TRIAL REGISTRATION: ISRCTN14931270 (retrospectively registered on 23/03/2018).

Serum Potassium Profile and Associated Factors in Incident Peritoneal Dialysis Patients.

BACKGROUND/AIMS: Abnormal potassium profiles are common in peritoneal dialysis (PD) patients. We studied the factors associated with serum potassium profiles in incident PD patients. METHODS: Patients were enrolled from two hospital-facilitated PD centers from May 2013 to May 2016 and January 2009 to December 2015. A total of 319 incident PD patients were examined for factors associated with serum potassium profile. Average serum potassium levels were obtained for analysis during the first 3 months after PD initiation. Clinically factors and parameters associated with PD were assessed by logistic regression. RESULTS: There were 168 men and 151 women (mean age, 50.8 years). Blood urea nitrogen (BUN), creatinine (Cr), and intact parathyroid hormone levels were significantly increased in patients in the higher serum potassium group. There were no significant risk factors for hypokalemia, including sex, age, diabetes, blood examination parameters, medication use, or PD-related parameters by multivariate logistic regression analysis. BUN (adjusted odds ratio [OR] 1.02, 95% CI 1.01-1.03, p = 0.001) and Cr (adjusted OR 1.08, 95% CI 1.01-1.16, p = 0.029) levels were significant risk factors for hyperkalemia by multivariate logistic regression analysis. CONCLUSION: Hyperkalemia and blood BUN and Cr levels were significantly associated in incident PD patients.

Serum Alkaline Phosphatase Levels are Not Associated with Increased Death Risk in Prevalent Hemodialysis Patients: 5-Year Experience in a Single Hemodialysis Center.

BACKGROUND/AIMS: Although high serum alkaline phosphatase (ALP) levels were reported as predictive factors for death risk in dialysis patients on the basis of large databank analyses, the real scenario in a single hemodialysis (HD) center is unknown. METHODS: In this study, a 5-year cohort of 1126 prevalent HD patients in the largest HD center in Taiwan was studied. The associations of ALP levels expressed as baseline, time-average, and time-dependent with all-cause mortality and cardiovascular mortality were evaluated by using adjusted Cox regression models. RESULTS: At baseline, levels of serum parathyroid hormone, calcium, and liver enzymes are increased in parallel with ALP quartiles. The hazard ratio (HR) for all-cause mortality was significantly increased in time-average and time-dependent ALP quartile in the unadjusted Cox analysis. The significance disappeared when multivariate adjusted Cox analysis was used. Similarly, HR was not significantly increased for cardiovascular mortality with ALP quartile expressed as baseline, time-average, and time-dependent in three models of Cox analyses. CONCLUSION: Our study demonstrated that serum ALP levels were not associated with increased death risk in prevalent HD patients over a 5-year interval.

An association between time-varying serum albumin level and the mortality rate in maintenance haemodialysis patients: a five-year clinical cohort study.

BACKGROUND: Until now, no long-term studies relating serum albumin level to mortality rate in prevalent haemodialysis (HD) patients have been conducted. We aimed to examine the association between serum albumin level and mortality over a 5-year period. METHODS: This study included 781 patients who received maintenance HD in a large, hospital-facilitated HD centre. Five-year medical records (2009-2013) were retrospectively reviewed, and the cut-off level for serum albumin level was set at 3.5 g/dL. The analysed albumin levels were expressed as time-averaged levels (first 24-month data) and albumin target reach rate over the first 2-year interval. Univariate and multivariate Cox proportional hazard regression models were used to examine the hazard function of the all-cause and cardiovascular mortality of the study participants in the subsequent 3-year period (2011-2013). RESULTS: Compared to those with a 100 % albumin reach rate (3.5 g/dL), the participants with 75- < 100, 50- < 75, and 1- < 50 % albumin reach rates exhibited significantly increased risk for all-cause mortality (HR 1.72, 95 % CI 1.19-2.47; HR 3.14, 95 % CI 1.91-5.16; HR 3.66, 95 % CI 2.18-6.16, respectively). A similar trend for all-cause mortality was demonstrated in participants with time-averaged albumin levels <4 g/dL (HR 1.57, 95 % CI 1.00-2.46 for 3.5-4.0 g/dL; HR 3.66, 95 % CI 2.11-6.32 for <3.5 g/dL). Compared to a 100 % albumin reach rate, the 50- < 75 and 1- < 50 % groups (HR 4.28, 95 % CI 1.82-10.01; HR 3.23, 95 % CI 1.22-8.54 respectively) showed significantly higher cardiovascular mortality rates. Similarly, participants with a time-averaged serum albumin level <3.5 g/dL exhibited a higher risk for cardiovascular mortality (HR 3.24, 95 % CI: 1.23-8.56). CONCLUSIONS: This long-term study demonstrated that higher reach rates of serum albumin levels and higher time-averaged serum albumin levels are associated with a lower mortality rate in patients undergoing maintenance HD.

Associations of mitochondrial haplogroups b4 and e with biliary atresia and differential susceptibility to hydrophobic bile Acid.

Mitochondrial dysfunction has been implicated in the pathogenesis of biliary atresia (BA). This study aimed to determine whether a specific mitochondrial DNA haplogroup is implicated in the pathogenesis and prognosis of BA. We determined 40 mitochondrial single nucleotide polymorphisms in 15 major mitochondrial haplogroups by the use of 24-plex PCR and fluorescent beads combined with sequence-specific oligonucleotide probes in 71 patients with BA and in 200 controls in the Taiwanese population of ethnic Chinese background. The haplogroup B4 and E prevalence were significantly lower and higher respectively, in the patients with BA than in the controls (odds ratios, 0.82 [p = 0.007] and 7.36 [p = 0.032] respectively) in multivariate logistic-regression analysis. The 3-year survival rate with native liver was significantly lower in haplogroup E than the other haplogroups (P = 0.037). A cytoplasmic hybrid (cybrid) was obtained from human 143B osteosarcoma cells devoid of mtDNA (ρ(0) cell) and was fused with specific mtDNA bearing E and B4 haplogroups donated by healthy Taiwanese subjects. Chenodeoxycholic acid treatment resulted in significantly lower free radical production, higher mitochondrial membrane potential, more viable cells, and fewer apoptotic cybrid B4 cells than parental 143B and cybrid E cells. Bile acid treatment resulted in a significantly greater protective mitochondrial reaction with significantly higher mitochondrial DNA copy number and mitofusin 1 and 2 concentrations in cybrid B4 and parental cells than in cybrid E cells. The results of the study suggested that the specific mitochondrial DNA haplogroups B4 and E were not only associated with lower and higher prevalence of BA respectively, in the study population, but also with differential susceptibility to hydrophobic bile acid in the cybrid harboring different haplogroups.

Indoxyl sulfate-induced oxidative stress, mitochondrial dysfunction, and impaired biogenesis are partly protected by vitamin C and N-acetylcysteine.

Indoxyl sulfate (IS) contributes to oxidative stress and endothelial dysfunction in chronic kidney disease patients. However, the role of mitochondria in IS-induced oxidative stress is not very clear. In this study, we examined whether mitochondria play a pivotal role in modulating the effects of antioxidants during IS treatment. In the context of human umbilical vein endothelial cells, we found that IS had a dose-dependent antiproliferative effect. In addition, we used flow cytometry to demonstrate that the level of reactive oxygen species increased in a dose-dependent manner after treatment with IS. High doses of IS also corresponded to increased mitochondrial depolarization and decreased mitochondrial DNA copy number and mitochondrial mass. However, these effects could be reversed by the addition of antioxidants, namely, vitamin C and N-acetylcysteine. Thus, our results suggest that IS-induced oxidative stress and antiproliferative effect can be attributed to mitochondrial dysfunction and impaired biogenesis and that these processes can be protected by treatment with antioxidants.