Glycated albumin to glycated hemoglobin ratio and mortality in diabetic patients on dialysis: a new association.

BACKGROUND: Hemoglobin A1c (A1c) and glycated albumin (GA) are two blood glycated proteins commonly used to monitor glycemic control in dialysis patients with diabetes. However, little is known about the association between the GA/A1c ratio and mortality in these populations. Here, we examine these associations using a nationwide cohort. METHODS: We enrolled 28 994 dialysis patients with diabetes who met our inclusion criteria (female, 32.9%; mean age, 67.4 ± 11.6 years; mean dialysis duration, 6.3 ± 5.8 years). After dividing the patients into groups based on GA/A1c quantiles and adjusting for 18 potential confounders, adjusted hazard ratios (HR) and 95% confidence limits were calculated for 3-year mortality and cause-specific mortalities. Additionally, propensity score matching analyses were used to compare mortalities between the low and high GA/A1c groups. RESULTS: After adjusting for possible confounders, significantly increased mortality was found in patients with GA/A1c ratios of 3.6-4.0 [HR 1.21 (1.10-1.34)] or higher [HR 1.43 (1.30-1.58)] than in those with GA/A1c ratios of 3.0-3.3. The risks of infectious and cardiovascular death were higher in these patients regardless of their nutritional status. In the propensity score matching analyses, significantly increased mortality was consistently found in those with a higher ratio (≥3.3) [HR 1.23 (1.14-1.33)] than in those with a lower ratio. CONCLUSIONS: The GA/A1c ratio was significantly associated with 3-year mortality, especially infectious and cardiovascular mortality, in dialysis patients with diabetes. This ratio may be a promising new clinical indicator of survival in these patients, independent of their current glycemic control and nutritional markers.

Novel Capped-Needle Device: A Novel Safety Feature to Eliminate Air Bubbles in Hemodialysis.

INTRODUCTION: Air bubbles in the dialysis circuit are rarely visible after automatic priming; however, they are often visible after the needles are manually connected to the circuit. To prevent this issue, we thought to prime needles with a circuit at automatic priming by the hemodialysis machine. In order to achieve this idea, we designed and manufactured a novel capped needle to connect the needles to the extracorporeal circuit before the automatic priming of the hemodialysis machine. This study investigated the effectiveness of this novel capped needle and compared it with the conventional method for preventing air bubble contamination. METHODS: We tested novel capped needles ten times to evaluate whether the dialysis machine works appropriately and removes air bubbles even with the attached capped needle. Next, we performed 25 trials using the conventional method, in which skilled nurses manually connect the needle. In both methods, we thoroughly counted the air bubbles with our naked eyes. We predicted that the capped needle would leave few bubbles in the circuit. In order to evaluate fewer bubbles, we conducted an additional experiment using a microparticle counter to measure the size and number of the bubbles. RESULTS: We thoroughly searched for air bubbles during each of the ten tests but could not find any bubbles visible to the naked eye. In the conventional method, bubbles were visible in 29 out of 50 cases. The bubble count was significantly lower in the capped-needle method than in the conventional method (p < 0.0001, Pearson's χ2 test). In the additional experiments using the microparticle counter, the average remaining air volume in the extracorporeal circuit was 0.0999 ± 0.2438 nL when the priming was performed using the novel capped needles. CONCLUSION: The novel capped needle eliminated all visible bubbles efficiently and effectively; therefore, it could be a valuable device for hemodialysis treatment. The reduction of air from the dialysis circuit may improve patient prognosis.

Chitin powder enhances growth factor production and therapeutic effects of mesenchymal stem cells in a chronic kidney disease rat model.

Previously, we fabricated a device with polylactic acid nonwoven filters and mesenchymal stem cells (MSCs), which effectively reduced urinary protein levels in a rat model of chronic kidney disease (CKD) but could not suppress CKD progression. Therefore, to improve the therapeutic effects of MSCs, in this study, we analyzed the ability of rat adipose tissue-derived MSCs (ADSCs) in contact with chitin nonwoven filters or chitin powder to produce growth factors and examined their therapeutic effect in an adriamycin (ADR)-induced CKD rat model. Hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) production was significantly enhanced by ADSCs cultured in a medium containing chitin powder (C-ADSCs) compared with that by ADSCs cultured in a standard medium without chitin (N-ADSCs). However, the production of HGF and VEGF by ADSCs on chitin nonwoven filters was not significantly enhanced compared with that by the control. Intravenous C-ADSC injection significantly increased podocin expression and improved proteinuria compared with those in saline-treated CKD rats; however, no such improvements were observed in the N-ADSC-treated group. These results showed that ADSCs cultured in a medium supplemented with chitin powder suppressed proteinuria via enhanced HGF and VEGF production in ADR-induced CKD rats to mitigate podocyte damage, offering a new strategy to reduce the dose of MSC therapy for safe and effective treatment of kidney disease.

Body fluid volume calculated using the uric acid kinetic model relates to the vascular event.

PURPOSE: We developed a method to measure the extracellular and intracellular fluid volumes using the kinetics of uric acid in the bodies of Japanese patients undergoing dialysis. In this research, we aimed to assess the prognosis of vascular events using this uric acid kinetic model method. METHODS: We conducted a retrospective cohort study of 1,298 patients who were undergoing hemodialysis or predilution online hemodiafiltration at the end of December 2019 at 13 institutions in Japan. Information on vascular events was acquired in 2020. Vascular event prognosis was defined as the new incidence of one or more of the following four types of vascular events: myocardial infarction, cerebral infarction, cerebral hemorrhage, or limb amputation. We measured the extracellular fluid volume and intracellular fluid volume after dialysis using the uric acid kinetic model method and determined the association between ECV, ICV, and vascular event risk. RESULTS: A high extracellular volume was substantially linked to an increased risk of vascular events. In addition, while a crude analysis revealed that a high intracellular volume was associated with a low risk of vascular events, this was not statistically significant after multifactorial adjustment. This result was partly affected by the low measurement accuracy of the serum urea nitrogen level used for the intracellular volume calculation. CONCLUSIONS: Extracellular volume calculated using the uric acid kinetic model method is a prognostic factor for vascular events in patients undergoing hemodialysis.

[A MULTICENTER CLINICAL SURVEY ABOUT THE PREVALENCE OF JAPANESE CYPRESS POLLINOSIS AND THE EFFICACY OF SUBLINGUAL IMMUNOTHERAPY WITH JAPANESE CEDAR POLLEN EXTRACT DURING JAPANESE CYPRESS POLLEN DISPERSAL PERIOD].

BACKGROUND: Little is known whether sublingual immunotherapy using Japanese cedar pollen extract (cedar SLIT) is effective for not only Japanese cedar pollinosis but also Japanese cypress pollinosis. We investigated the prevalence rate of Japanese cypress pollinosis, efficacy of cedar SLIT on cypress pollinosis and patients' wish to receive cypress SLIT. METHODS: We investigated a multi-center (31 institutions), cross-sectional survey using a self-administrated questionnaire with four questions for patients received cedar SLIT aged from 5 to 69 years old. RESULTS: 2523 subjects were enrolled for analysis. 83.4% of them had pollinosis symptoms during cypress season before cedar SLIT. In such patients, 37.4% experienced lessened efficacy of cedar SLIT during cypress season. Both the prevalence of cypress pollinosis and the lessened efficacy of cedar SLIT on cypress pollinosis were significantly seen in western Japan as compared to eastern Japan. 76.1% of the subject having cypress pollinosis before SLIT wished to receive cypress SLIT if it is available. CONCLUSION: A lessened efficacy of cedar SLIT during cypress season was broadly seen in Japan, and further showed a regional difference. Together with the finding of high wish by patients, these results suggest a development of cypress SLIT is desirable.

A multiple 24-hour urine collection study indicates that kidney function decline is related to urinary sodium and potassium excretion in patients with chronic kidney disease.

Multiple 24-hour urine collections are necessary to adequately assess sodium and potassium intake. Here, we assessed kidney function decline for four years after baseline in relation to seven-time averaged 24-hour urinary sodium and potassium excretion (UNaV, UKV), their UNaV/UKV ratio, and their categorical combination in outpatients with chronic kidney disease (CKD). This retrospective cohort study was based on 240 outpatients with baseline CKD stages 3-5, baseline age 20 years or more (median age 72.0 years), and a median follow-up (with interquartile range) of 2.9 (1.4-4.0) years. Outcome was the percentage change in annual slope of estimated glomerular filtration rate (delta eGFR per year). In linear mixed models, percentage changes in delta eGFR per year were -3.26% (95% confidence interval -5.85 to -0.60), +5.20% (2.34 to 8.14), and -5.20% (-7.64 to -2.69), respectively, per one standard deviation increase in the seven-time averaged UNaV and UKV, and their UNaV/UKV ratio. Additionally, percentage changes per year in delta eGFR per year were -16.27% (-23.57 to -8.27) in the middle-to-high UNaV and low UKV group, compared with the low UNaV and middle-to high UKV group. Thus, our study reinforces the observation of opposite associations between GFR decline and urinary excretion rates of sodium (positive) and potassium (negative), respectively. Whether changes in dietary sodium and potassium intake slow GFR decline still requires further study.

Comparison of Body Fluid Volumes Determined by Kinetic Modeling and by Bioimpedance Spectroscopy.

INTRODUCTION: The bioimpedance spectroscopy (BIS) method is used in individual patients requiring body fluid volume measurement. In a hemodialysis facility, however, regular screening of body fluid volumes is also necessary. Such screening, by kinetic modeling, may become possible by calculating distribution volumes of urea and uric acid from regular blood test results. OBJECTIVE: The aim is to compare uric acid distribution volumes with BIS-extracellular volume, urea distribution volume with BIS-total body water, and difference between urea and uric acid distribution volumes with BIS-intracellular volume. METHODS: We reanalyzed stored blood test data of 53 hemodialysis patients obtained together with BIS data of the same patients in our previous study. RESULTS: Significant correlations were found between urea distribution volume and total body water predicted by the BIS method, between uric acid distribution volume and extracellular volume predicted by the BIS method, and between the difference of uric acid distribution volume from urea distribution volume and intracellular volume predicted by the BIS method. In Bland-Altman analysis, comparison of each pair showed no systematic error. The mean difference between each pair was minimal. CONCLUSION: Fluid volumes in different body compartments can be estimated by kinetic modeling as well as by the BIS method.

Predilution online hemodiafiltration is associated with improved survival compared with hemodialysis.

On-line hemodiafiltration is an increasingly common alternative to chronic hemodialysis in some countries, based on the results of randomized controlled trials of post-dilution on-line hemodiafiltration. There are now more than 60,000 patients treated with on-line hemodialfiltration in Japan, over 95% of whom use predilution on-line hemodiafiltration; however, large-scale data on clinical outcomes with this modality are lacking. We created a propensity-matched cohort of 5,000 pairs of patients treated with conventional hemodialysis or predilution on-line hemodiafiltration, using the Japanese Society for Dialysis Therapy Renal Data Registry database from December 31, 2012 to December 31, 2013. One-year all-cause and cardiovascular mortality were compared between the groups. Predilution on-line hemodiafiltration was associated with improved overall survival compared to hemodialysis (hazard ratio for all cause-mortality 0.83, 95% confidence interval 0.705-0.986), with a trend towards improved cardiovascular survival. Among patients treated with predilution on-line hemodiafiltration, those treated with high substitution volumes (≥40.0 L per session) had improved all-cause and cardiovascular survival compared to those treated with low substitution volumes (<40.0 L per session) or those on hemodialysis. The optimal substitution volume associated with improved overall survival was estimated to be 50.5 L [95% confidence interval 39.0-63.5 L]. This observational study suggests that predilution on-line hemodiafiltration, especially with high substitution volumes, may improve all-cause and cardiovascular survival, but randomized controlled trials are needed.

Glycated albumin versus hemoglobin A1c and mortality in diabetic hemodialysis patients: a cohort study.

Background: For glycemic control in diabetic patients on dialysis it was unclear what level of glycated albumin (GA) was associated with the lowest mortality and GA's utility. Accordingly, we examined the difference in association between GA and hemoglobin A1c (HbA1c) with 1-year mortality in a cohort of the Japanese Society for Dialysis Therapy. Methods: We examined 84 282 patients with prevalent diabetes who were on maintenance hemodialysis (HD) (female 30.3%; mean age 67.3 ± 11.2 years; mean dialysis vintage 6.4 ± 4.5 years). Of them, 22 441 had both GA and HbA1c. We followed these for a year, 2013-14, using Cox regression to calculate adjusted hazard ratios (HRs) and 95% confidence limits for 1-year mortality after adjusting for potential confounders such as baseline age, sex, smoking and diabetes type. Results: One-year mortality was lowest in diabetic HD patients who had GA levels of 15.6-18.2% and HbA1c levels of 5.8-6.3%. The associations were linear or J-shaped for GA and U-shaped for HbA1c. Adjusted HRs were significantly higher in patients with GA <12.5% and GA ≥22.9%. This trend flattened in elderly patients, those with higher hemoglobin or those with prior cardiovascular disease. In addition, the C-statistics, Harrell's C and category-free net reclassification improvement to predict 1-year mortality were better when GA was added to the model than when HbA1c was added. Conclusions: There was a linear or J-shaped association between GA and 1-year mortality, with the lowest mortality at GA 15.6-18.2%. Furthermore, our analyses suggest the potential superiority of GA over HbA1c in predicting mortality.

High-Performance Membrane Dialyzers and Mortality in Hemodialysis Patients: A 2-Year Cohort Study from the Annual Survey of the Japanese Renal Data Registry.

BACKGROUND: Little information is available regarding the type of dialyzer which results in good prognosis. This study is aimed at investigating the association between 7 types of dialyzers and 2-year mortality. METHODS: We conducted a cohort study using data from a nationwide registry of the Japanese Society for Dialysis Therapy. Subjects were 136,676 patients on maintenance hemodialysis (HD) between 2009 and 2011 who underwent maintenance HD for at least 2 years and were treated with one of the following 7 types of high-performance membrane dialyzers: cellulose triacetate (CTA), ethylene vinyl alcohol (EVAL), polyacrylonitrile (PAN), polyester polymer alloy (PEPA), polyethersulfone (PES), polymethylmethacrylate (PMMA), and polysulfone (PS). Cox regression was used to estimate the association between baseline dialyzers and all-cause 2-year mortality, adjusting for potential confounders. RESULTS: Data were adjusted using basic factors, with PS as a reference group, and the hazard ratio (HR) was significantly higher in CTA, PMMA, PAN, and EVAL groups. Further data adjustment for Kt/V yielded the same results as were obtained from data adjusted for basic factors. After further adjustment for nutrition- and inflammation-related factors, HR was significantly lowered for the PES and PMMA groups compared with the PS group (HR 0.88; 95% CI 0.82-0.94 and HR 0.84 95% CI 0.76-0.93, respectively). After propensity score matching, HR for the PES and PMMA groups was significantly lowered compared with the PS group. CONCLUSIONS: The use of different membrane types may affect mortality. Further long-term prospective studies are needed to clarify whether the PES and PMMA membranes can improve prognosis.

Significance of the decreased risk of dialysis-related amyloidosis now proven by results from Japanese nationwide surveys in 1998 and 2010.

BACKGROUND: Although dialysis technology greatly improved in recent years, it remained unclear whether those improvements helped decrease the incidence of dialysis-related amyloidosis (DRA). Accordingly, we retrospectively compared the incidence of first-time carpal tunnel surgery (CTS)-as proxy for DRA onset-in two cohorts of chronic hemodialysis patients, with the second cohort studied after dialysis methods (especially dialyzate quality control) had greatly improved. METHODS: We used the 1998 and 2010 Japan Renal Data Registries to compare crude risk of first-time CTS the following year. After adjusting for patient background and laboratory data, odds ratios (ORs) for CTS in the whole cohorts and the populations matched by propensity score (PS) for hemodialysis and hemodiafiltration were calculated at a 95% confidence interval. RESULTS: Of note, 2 02 726 patients were analyzed. In the 1998 cohort, 1.77% experienced first-time CTS compared with 1.30% of the 2010 cohort (P < 0.001); with 2010 as referent, the adjusted 1998 OR was 2.22 (1.68-2.95). Both crude risks and adjusted ORs were analyzed by dialysis vintage, age, pre-dialysis ß2-microglobulin (ß2m) and ß2m clearance, risk of CTS trending 1.5-2.0 higher in 1998 than 2010. The reduction was most prominent in patients with longer dialysis vintage, patients who were younger, and those with lower pre-dialysis ß2m levels. Similar results were obtained by PS-matched analysis. We also found that ß2m clearance >80% may reduce risk of CTS. CONCLUSIONS: The incidence of first-time CTS as proxy for DRA decreased significantly from 1998 to 2010. Several factors may have contributed to this decrease, including improved dialysis methods.

Toward the treatment for Alzheimer's disease: adsorption is primary mechanism of removing amyloid ß protein with hollow-fiber dialyzers of the suitable materials, polysulfone and polymethyl methacrylate.

The accumulation of amyloid ß protein (Aß) in the brain reflects cognitive impairment in Alzheimer's disease. We hypothesized that the rapid removal of Aß from the blood by an extracorporeal system may act as a peripheral Aß sink from the brain. The present study aimed to determine the optimal materials and modality for Aß removal by hemodialyzers. In a batch analysis, hollow-fiber fragments of polysulfone (PSf) and polymethyl methacrylate (PMMA) showed greater removal efficiency of Aß than did other materials, such as cellulose-triacetates and ethylene-vinyl alcohol copolymer (PSf:PMMA at 30 min, 98.6 ± 2.4 %:97.8 ± 0.4 % for Aß1-40 and 96.6 ± 0.3 %:99.0 ± 1.0 % for Aß1-42). In a modality study, the Aß solution was applied to PSf dialyzers and circulated in the dialysis and Air-filled adsorption-mode (i.e., the outer space of the hollow fibers was filled with air) or phosphate-buffered saline (PBS)-filled adsorption modes. The Aß1-40 removal efficiency of the pre/post dialyzer in the Air-filled adsorption-mode was the highest (62.4 ± 12.6 %, p = 0.007). In a flow rate study in the Air-filled adsorption-mode, 200 mL/min showed the highest Aß1-40 reduction rate of pool solution (97.3 ± 0.8 % at 15 min) compared with 20 mL/min (p = 0.00001) and 50 mL/min (p = 0.00382). PMMA dialyzers showed similar high reduction rates. Thus, the optimal modality for Aß removal was the adsorption-mode with PSf or PMMA hollow fibers at around 50 mL/min flow rate, which seems to be suitable for clinical use.

Dialysis fluid endotoxin level and mortality in maintenance hemodialysis: a nationwide cohort study.

BACKGROUND: The quality of dialysis fluid water might play an important role in hemodialysis patient outcomes. Although targeted endotoxin levels of dialysis fluid vary among countries, evidence of the contribution of these levels to mortality in hemodialysis patients is lacking. STUDY DESIGN: Retrospective cohort study using data from the Japan Renal Data Registry, a nationwide annual survey. SETTING & PARTICIPANTS: 130,781 patients receiving thrice-weekly in-center hemodialysis for more than 6 months were enrolled at 2,746 facilities in Japan at the end of 2006. None of the patients changed facility or treatment modality during 2007. PREDICTOR: Highest endotoxin level in dialysis fluid reported by each facility during 2006. Patients were categorized by facility endotoxin level into the following groups: <0.001, 0.001 to <0.01, 0.01 to <0.05, 0.05 to <0.1, and ≥0.1EU/mL. Age, sex, dialysis vintage, diabetes mellitus as a primary cause of end-stage renal disease, Kt/V, normalized protein catabolic rate, dialysis session duration, serum albumin, and hemoglobin were measured as potential confounders. OUTCOME: All-cause mortality, censored by transplantation; withdrawal from dialysis treatment; or end of follow-up. RESULTS: Of 130,781 hemodialysis patients, 91.2% had facility endotoxin levels below the limit set for dialysis fluid in Japan (<0.05EU/mL). During a 1-year follow-up, 8,978 (6.9%) patients died of all causes. The rate of all-cause mortality at 1 year was highest in the ≥0.1-EU/mL category (88.0 deaths/1,000 person-years). Patients in the ≥0.1-EU/mL group exhibited an increased risk of all-cause mortality of 28% (95% CI, 10%-48%) compared to the <0.001-EU/mL group. LIMITATIONS: Endotoxin level in dialysis fluid is reported as categorical data. No information about variation in endotoxin levels in dialysis fluid over time. CONCLUSIONS: Higher facility endotoxin levels in dialysis fluid may be related to increased risk for all-cause mortality among hemodialysis patients. Correcting this modifiable facility water management practice might improve the outcome of hemodialysis patients.

Prevalence and incidence of chronic kidney disease stage G5 in Japan.

The prevalence and incidence of end-stage kidney disease (ESKD) have continued to increase worldwide. Japan was known as having the highest prevalence of ESKD in the world; however, Taiwan took this place in 2001, with the USA still in third position. However, the prevalence data from Japan and Taiwan consisted of dialysis patients only. The prevalence and incidence of Kidney Transplantation (KT) in Japan were quite low, and the number of KT patients among those with ESKD was regarded as negligibly small. However, the number of KT recipients has increased recently. Furthermore, there are no reports about nationwide surveys on the prevalence and incidence of predialysis chronic kidney failure patients in Japan. This review describes our recent study on the estimated number of chronic kidney disease (CKD) stage G5 patients and the number of ESKD patients living in Japan, obtained via the cooperation of five related medical societies. From the results, as of Dec 31, 2007, 275,242 patients had received dialysis therapy and 10,013 patients had a functional transplanted kidney, and as of Dec 31, 2008, 286,406 patients had received dialysis therapy and 11,157 patients had a functional transplanted kidney. Consequently, there were 285,255 patients with CKD who reached ESKD and were living in Japan in 2008 and 297,563 in 2009. We also estimated that there were 67,000 predialysis CKD stage G5 patients in 2009, 37,365 patients introduced to dialysis therapy, and 101 patients who received pre-emptive renal transplantation in this year. In total, there were 37,466 patients who newly required renal replacement therapy (RRT) in 2009. Not only the average ages, but also the primary renal diseases of the new ESKD patients in each RRT modality were different.

Appropriate nonwoven filters effectively capture human peripheral blood cells and mesenchymal stem cells, which show enhanced production of growth factors.

Scaffolds, growth factors, and cells are three essential components in regenerative medicine. Nonwoven filters, which capture cells, provide a scaffold that localizes and concentrates cells near injured tissues. Further, the cells captured on the filters are expected to serve as a local supply of growth factors. In this study, we investigated the growth factors produced by cells captured on nonwoven filters. Nonwoven filters made of polyethylene terephthalate (PET), biodegradable polylactic acid (PLA), or chitin (1.2-22 µm fiber diameter) were cut out as 13 mm disks and placed into cell-capturing devices. Human mesenchymal stem cells derived from adipose tissues (h-ASCs) and peripheral blood cells (h-PBCs) were captured on the filter and cultured to evaluate growth factor production. The cell-capture rates strongly depended on the fiber diameter and the number of filter disks. Nonwoven filter disks were composed of PET or PLA fibers with fiber diameters of 1.2-1.8 µm captured over 70% of leukocytes or 90% of h-ASCs added. The production of vascular endothelial growth factor (VEGF), transforming growth factor ß1, and platelet-derived growth factor AB were significantly enhanced by the h-PBCs captured on PET or PLA filters. h-ASCs on PLA filters showed significantly enhanced production of VEGF. These enhancements varied with the combination of the nonwoven filter and cells. Because of the enhanced growth factor production, the proliferation of human fibroblasts increased in conditioned medium from h-PBCs on PET filters. This device consisting of nonwoven filters and cells should be investigated further for possible use in the regeneration of impaired tissues.

Carpal tunnel surgery as proxy for dialysis-related amyloidosis: results from the Japanese society for dialysis therapy.

BACKGROUND/AIMS: This study aims to identify current risk factors for developing dialysis-related amyloidosis using carpal tunnel syndrome (CTS) as proxy for general amyloidosis. METHODS: The cohort consisted of 166,237 patients on dialysis (mean age 66.1 ± 12.4 years; mean dialysis vintage 7.2 ± 6.4 years) who could be followed for a year between 2010 and 2011. Of these, 2,157 (1.30%) needed first-time CTS surgery during the study period. Odds ratios (ORs) for CTS were calculated at a 95% confidence interval (95% CI) after adjusting for age, gender, primary kidney disease, history of smoking, history of hypertension vintage, dialysis modality, use of high-flux membrane, body mass index, serum albumin, Kt/V, normalized protein catabolic rate, C-reactive protein, pretreatment ß2-microglobulin (ß2MG), and ß2MG clearance. RESULTS: Adjusted ORs of first-time CTS for vintages 10-15, 15-20, 20-25 (referent), 25-30, and >30 years were, respectively, 0.18 (0.12-0.26), 0.43 (0.31-0.62), 1.00, 2.37 (1.64-3.40), and 3.87 (2.52-5.93). Adjusted ORs for ages 40-50, 50-60 (referent), 60-70, 70-80, and >80 were 0.53 (0.30-0.94), 1.00, 1.89 (1.41-2.52), 1.52 (1.08-2.14), and 1.04 (0.60-1.80). Female gender, low serum albumin, and diabetic nephropathy were also associated with CTS. Pretreatment serum ß2MG and ß2MG clearance <80% were not significant, although ß2MG clearance >80% was negatively associated with CTS [OR 0.34 (0.13-0.90)]. CONCLUSION: ORs of first-time CTS almost doubled with every 5-year increase in dialysis vintage. ORs of CTS were highest for patients aged 60-70. Other factors associated with CTS were gender, serum albumin, and diabetic nephropathy. ß2MG clearance >80% may decrease the incidence of CTS.

Current dialyzer classification in Japan and mortality risk in patients undergoing hemodialysis.

Dialyzers are classified into five types based on their ß2-microglobulin clearance rate and albumin sieving coefficient: Ia, Ib, IIa, and IIb. In addition, a new classification system introduced a type S dialyzer. However, limited information is available regarding the impact of dialyzer type on patient outcomes. A cohort study was conducted using data from the Japanese Society for Dialysis Therapy Renal Data Registry database. Total 181,804 patients on hemodialysis (HD) were included in the study, categorized into four groups (type Ia, IIa, IIb, and S). The associations between each group and two-year all-cause mortality were assessed using Cox proportional hazard models. Furthermore, propensity score-matching analysis was performed. By the end of 2019, 34,185 patients on dialysis had died. After adjusting for all confounders, the risk for all-cause mortality was significantly lower in the type IIa, and S groups than in the type Ia group. These significant findings were consistent after propensity score matching. In conclusion, our findings suggest that super high-flux dialyzers, with a ß2-microglobulin clearance of ≥ 70 mL/min, may be beneficial for patients on HD, regardless of their albumin sieving coefficient. In addition, type S dialyzers may be beneficial for elderly and malnourished patients on dialysis.Trial registration number: UMIN000018641.

Comparison of effective impact among tonsillectomy alone, tonsillectomy combined with oral steroid and with steroid pulse therapy on long-term outcome of immunoglobulin A nephropathy.

BACKGROUND: To clarify the therapeutic impact of tonsillectomy and combined therapies of tonsillectomy plus steroid on the long-term prognosis of immunoglobulin A nephropathy (IgAN). METHODS: A retrospective study was conducted on 208 patients with IgAN between 1986 and 2009. According to the strategies for treatments, patients were divided into four groups: tonsillectomy and steroid pulse (TSP, n = 47), tonsillectomy and oral steroid (TOS, n = 33), tonsillectomy alone (T, n = 56), and N group (no particular therapy, n = 72). Multivariate analysis based on the Cox's regression model was used to assess the relative risk of reaching the outcome of doubling creatinine based on the influence of baseline prognostic factors. RESULTS: The mean observation periods were 53.8 months in the TSP group, 122.0 months in the TOS group, 102.9 months in the T group, and 84.6 months in the N group. During an observation period, serum creatinine levels doubled as follows: one in the TSP group (2.1 %), two in the TOS group (6.1 %), five in the T group (8.9 %), histological severity, and 22 in the N group (30.6 %). The Cox's regression proportional hazard model showed that gender, age, histological activity, dialysis induction risk and therapy were associated with doubling creatinine levels. Hazard ratios (95 % CI) and (P value) in T, TOS, and TSP groups versus N were 0.314 (0.11-0.93, P = 0.037), 0.213 (0.04-1.10, P = 0.065), and 0.032 (0.00-0.28, P = 0.002), respectively. CONCLUSION: A combination therapy of tonsillectomy and steroid pulse had the most significant therapeutic impact compared to other therapies.

Effects of N-acetyl-L-tryptophan on desorption of the protein-bound uremic toxin indoxyl sulfate and effects on uremic sarcopenia.

INTRODUCTION: Indoxyl sulfate (IS) is a protein-bound uremic toxin that causes uremic sarcopenia. IS has poor dialysis clearance; however, the addition of a binding competitor improves its removal efficiency. METHODS: Dialysis experiments were performed using N-acetyl-l-tryptophan (L-NAT) instead of l-tryptophan (Trp) using pooled sera obtained from dialysis patients. The molecular structures of L-NAT and Trp were similar to that of IS. Therefore, we examined whether Trp and L-NAT were involved in muscle atrophy in the same manner as IS by performing culture experiments using a human myotube cell line. RESULTS: The removal efficiency of L-NAT was the same as that of Trp. However, L-NAT concentrations in the pooled sera increased at the end of the experiment. Trp (1 mM) decreased the area of human myocytes, similar to IS, whereas L-NAT did not. CONCLUSION: L-NAT is a binding competitor with the ability to remove protein-bound IS while preventing sarcopenia.

Combination of brain natriuretic peptide and urinary albumin as a predictor of cardiovascular-renal events in outpatients with chronic kidney disease.

Objectives: Cardiovascular and renal diseases are closely related. Brain natriuretic peptide (BNP) and urinary albumin are established predictors for cardiac and renal morbidities, respectively. To date, no reports have investigated the combined predictive value of BNP and urinary albumin for long-term cardiovascular-renal events in patients with chronic kidney disease (CKD). The aim of this study was to investigate this theme. Methods: Four hundred eighty-three patients with CKD were enrolled into this study and followed-up for 10 years. The endpoint was cardiovascular-renal events. Results: During the median follow-up period of 109 months, 221 patients developed cardiovascular-renal events. Log-transformed BNP and urinary albumin were identified as independent predictors for cardiovascular-renal events, with a hazard ratio of 2.59 (95% confidence interval [CI], 1.81-3.72) and 2.27 (95% CI, 1.82-2.84) for BNP and urinary albumin, respectively. For the combined variables, the group with high BNP and urinary albumin had a markedly higher risk (12.41-times; 95% CI 5.23-29.42) of cardiovascular-renal events compared with that of the group with low BNP and urinary albumin. Adding both variables to a predictive model with basic risk factors improved the C-index (0.767, 0.728 to 0.814, p=0.009), net reclassification improvement (0.497, p<0.0001), and integrated discrimination improvement (0.071, p<0.0001) more than each of them alone. Conclusions: This is the first report to demonstrate that the combination of BNP and urinary albumin can stratify and improve the predictability of long-term cardiovascular-renal events in CKD patients.