Search

Background Higher serum β2-microglobulin (B2M) concentrations are associated with higher mortality in the general population, non-dialyzed chronic kidney disease patients and patients receiving hemodialysis (HD). However, this relationship among patients on peritoneal dialysis (PD) has not been validated. Methods We collected baseline data for 3,011 prevalent PD patients from a nationwide dialysis registry in Japan at the end of 2010. Clinical outcomes for 9 years were then evaluated using the registry at the end of 2011 to 2019. All-cause and cardiovascular (CV) mortality was assessed using Cox regression analysis and competing-risks regression analysis, respectively. We used multiple imputation to deal with missing covariate data. Results During a median follow-up of 87 months, 2,054 patients transferred to combined therapy with PD and HD or HD directly. A total of 3,011 patients, 1,235 (41.0%) died, including 437 patients (14.5%) from CV causes. Among them, 612 patients died after transfer to other dialysis modalities. Univariate analyses revealed no significant association between serum B2M and mortality, whereas higher serum B2M was independently associated with both all-cause and CV mortalities in adjusted models. However, the significant association between serum B2M and CV mortality disappeared in analysis treating serum B2M as a categorical variable. The effect of serum B2M on all-cause mortality was significantly higher among patients with higher urinary volume and a significant interaction was evident. Conclusions Using a large-scale registry, we found that serum B2M contributes tenuously but significantly to worse outcome and residual kidney function significantly affects this relationship. On the contrary, serum B2M per se had no predictive value for patient outcome in prevalent PD patients.

BackgroundFatigue is one of the most frequent complications in dialyzed patients and is associated with poorer patient outcomes. Multiple factors are reported to be associated with fatigue development. Of them, the impacts of dialysis modalities remain unknown.MethodsA total of 194 dialysis patients (mean age, 61±11 years; 134 males; modalities included hemodialysis (HD) in 26, online hemodiafiltration (HDF) in 74, peritoneal dialysis (PD) in 68, and combined therapy with PD and HD in 26 cases) were recruited for this cross-sectional study. Fatigue was assessed using the Profile of Mood States (POMS), a Visual Analogue Scale (VAS), and our original scale of fatigue, and depression was assessed by the Beck Depression Inventory-second edition (BDI-II). Our original scale of fatigue was administered both on dialysis and dialysis-free days to patients on HD and online HDF.ResultsThe scores of the POMS, VAS, and our original scale were weakly but significantly inter-related (rho = 0.58, PConclusionsThe results suggest that there is no significant association between different dialysis modalities including HD, online HDF, PD and combined therapy with PD and HD and the prevalence or severity of fatigue.

BackgroundHyperuricemia is highly prevalent in chronic kidney disease (CKD) patients, but the evidence for a relationship between uric acid (UA) and clinical outcomes in CKD patients is limited and inconsistent. We hypothesized that UA has a different impact on clinical outcomes according to the underlying disease causing CKD.MethodsThis study prospectively investigated the associations between UA and renal and non-renal outcomes according to the underlying disease causing CKD in 2,797 Japanese patients under the care of nephrologists. The patients were categorized into four groups: primary renal disease (n = 1306), hypertensive nephropathy (n = 467), diabetic nephropathy (n = 275), and other nephropathy (n = 749). The renal outcome was defined as end-stage renal disease (ESRD), and the non-renal outcome was defined as a composite endpoint of cardiovascular events (CVEs) and all-cause mortality.ResultsDuring a median 4.8-year follow-up, 359 (12.8%) patients reached the renal outcome, and 260 (9.3%) reached the non-renal outcome. In the all-patient analysis, hyperuricemia was not associated with the risks for renal and non-renal outcomes, but in primary renal disease (PRD) and hypertensive renal disease (HTN) patients, hyperuricemia was significantly associated with non-renal outcomes. Per 1 mg/dl higher UA level, multivariable adjusted hazard ratio was 1.248 (95% CI: 1.003 to 1.553) for PRD, and 1.250 (1.035 to 1.510) for HTN. Allopurinol did not reduce the risks for renal and non-renal outcomes, both in all patients and in the subgroup analysis.ConclusionsThe effect of hyperuricemia on clinical outcomes in CKD patients varies according to the underlying disease causing CKD. Hyperuricemia is an independent risk factor for non-renal outcomes in primary renal disease and hypertensive renal disease patients. Allopurinol did not decrease the risks for renal and non-renal outcomes.

It is supposed that enhanced oxidative stress and inflammation are involved with the poor clinical outcomes in patients on chronic dialysis treatment. Recent studies have shown that molecular hydrogen (H2) is biologically active as an anti-inflammatory agent. Thus, we developed a novel hemodialysis (E-HD) system which delivers H2 (30 to 80 ppb)-enriched dialysis solution, to conduct a prospective observational study (UMIN000004857) in order to compare the long-term outcomes between E-HD and conventional-HD (C-HD) in Japan. The present interim analysis aimed to look at potential clinical effects of E-HD during the first 12 months observation.262 patients (140, E-HD; 122, C-HD) were subjected for analysis for comprehensive clinical profiles. They were all participating in the above mentioned study, and they had been under the respective HD treatment for 12 consecutive months without hospitalization. Collected data, such as, physical and laboratory examinations, medications, and self-assessment questionnaires on subjective symptoms (i.e., fatigue and pruritus) were compared between the two groups.In a 12-month period, no clinical relevant differences were found in dialysis-related parameters between the two groups. However, there were differences in the defined daily dose of anti-hypertensive agents, and subjective symptoms, such as severe fatigue, and pruritus, which were all less in the E-HD group. Multivariate analysis revealed E-HD was an independent significant factor for the reduced use of anti-hypertensive agents as well as the absence of severe fatigue and pruritus at 12 months after adjusting for confounding factors.The data indicates E-HD could have substantial clinical benefits beyond conventional HD therapy, and support the rationale to conduct clinical trials of H2 application to HD treatment.

Electric brain stimulations such as transcranial direct current stimulation (tDCS), transcranial random noise stimulation (tRNS), and transcranial alternating current stimulation (tACS) electrophysiologically modulate brain activity and as a result sometimes modulate behavioral performances. These stimulations can be viewed from an engineering standpoint as involving an artificial electric source (DC, noise, or AC) attached to an impedance branch of a distributed parameter circuit. The distributed parameter circuit is an approximation of the brain and includes electric sources (neurons) and impedances (volume conductors). Such a brain model is linear, as is often the case with the electroencephalogram (EEG) forward model. Thus, the above-mentioned current stimulations change the current distribution in the brain depending on the locations of the electric sources in the brain. Now, if the attached artificial electric source were to be replaced with a resistor, or even a negative resistor, the resistor would also change the current distribution in the brain. In light of the superposition theorem, which holds for any linear electric circuit, attaching an electric source is different from attaching a resistor; the resistor affects each active electric source in the brain so as to increase (or decrease in some cases of a negative resistor) the current flowing out from each source. From an electrophysiological standpoint, the attached resistor can only control the extracellular impedance and never causes forced stimulation; we call this technique transcranial extracellular impedance control (tEIC). We conducted a behavioral experiment to evaluate tEIC and found evidence that it had real-time enhancement and depression effects on EEGs and a real-time facilitation effect on reaction times. Thus, tEIC could be another technique to modulate behavioral performance.

BACKGROUND: Advanced glycation end product (AGE) accumulation is thought to be a measure of cumulative metabolic stress that has been reported to independently predict cardiovascular disease in diabetes and renal failure. The aim of this study was to evaluate the association between AGE accumulation, measured as skin autofluorescence, and the progression of renal disease in pre-dialysis patients with chronic kidney disease (CKD). METHODS: Skin autofluorescence was measured noninvasively with an autofluorescence reader at baseline in 449 pre-dialysis patients with CKD. The primary end point was defined as a doubling of serum creatinine and/or need for dialysis. RESULTS: Thirty-three patients were lost to follow-up. Forty six patients reached the primary end point during the follow-up period (Median 39 months). Kaplan-Meier analysis showed a significantly higher risk of development of the primary end points in patients with skin autofluorescence levels above the optimal cut-off level of 2.31 arbitrary units, derived by receiver operator curve analysis. Cox regression analysis revealed that skin autofluorescence was an independent predictor of the primary end point, even after adjustment for age, gender, smoking history, diabetes, estimated glomerular filtration rate and proteinuria (adjusted hazard ratio 2.58, P = 0.004). CONCLUSIONS: Tissue accumulation of AGEs, measured as skin autofluorescence, is a strong and independent predictor of progression of CKD. Skin autofluorescence may be useful for risk stratification in this group of patients; further studies should clarify whether AGE accumulation could be one of the therapeutic targets to improve the prognosis of CKD.