BackgroundThe aim of this study was to clarify the current status of assisted peritoneal dialysis (PD) implementation in Japan.MethodsA nationwide, cross-sectional, questionnaire survey was conducted by the Working Group of the Academic Committee of the Japanese Society for Peritoneal Dialysis. A paper-based questionnaire of 22 items was developed based on a literature review and clinical experience. The questionnaires were sent to all 310 facilities that were members of the Japanese Society for Peritoneal Dialysis (JSPD).ResultsResponses were received from 209 facilities (response rate 67.4%). It was found that assisted PD is already being implemented in approximately two-thirds of PD facilities, accounting for 15.9% of all PD patients. Cognitive decline and muscle weakness were the leading reasons for starting assisted PD. Family members, particularly spouses and adult children, were the main caregivers in this cohort, either alone or in collaboration with visiting nurses; cooperation with general practitioners was relatively limited. Facilities with a large number of PD patients made use of collaboration with visiting nurses and respite care facilities, remote monitoring, and medical care-specific social networking sites.ConclusionThis nationwide survey demonstrates that assisted PD is widely practiced in Japan and plays a critical role in sustaining PD therapy for elderly and functionally impaired patients. However, substantial heterogeneity in implementation and insufficient integration with broader medical and social care systems remain major challenges. Addressing these issues through standardization, multidisciplinary collaboration, and policy reform will be essential to meet the needs of Japan's rapidly aging dialysis population.

Calcimimetics reduce mortality in older patients on dialysis. Because elderly patients are prone to low body mass index (BMI) and inflammation, we investigated whether this effect is independent of these conditions. This retrospective study used propensity score matching to compare 2-year all-cause mortality between calcimimetic users and non-users. Patients were stratified according to thresholds of BMI (22 kg/m(2)) and high-sensitivity C-reactive protein (hs-CRP; 0.3 mg/dL) into Group 1 (high BMI and low hs-CRP, n = 240) and Group 2 (low BMI and high hs-CRP, n = 498). Survival was assessed using Kaplan-Meier survival curves, censored for calcimimetic use and other covariates. In Group 2, mortality was significantly lower in calcimimetic users than in non-users after matching (P = 0.003, log-rank test), but not in Group 1. The significant difference in Group 2 was no longer observed after Cox proportional hazards regression adjusted for covariates that remained imbalanced following matching (P = 0.051). In Group 2, median age (69 years)-stratified analysis showed significantly lower mortality in users among older patients (hazard ratio, 0.206, 95% confidence interval, 0.058-0.728, P = 0.014), but not younger patients. These findings suggest an association between calcimimetic use and reduced mortality in elderly patients with low BMI and/or inflammation, but not in those without these conditions or in non-users.

Serum butyrylcholinesterase (BChE) levels are positively correlated with serum albumin levels and are influenced by inflammation. Heterozygous BChE deficiency in patients on dialysis may be overlooked as malnutrition owing to dialysis-associated low BChE and albumin levels. In this study, we aimed to clarify a method for identifying low BChE levels due to hereditary causes. This single-center, retrospective, observational study included 1,104 patients undergoing dialysis and 1,716 patients not undergoing dialysis. Patients on dialysis with available data of high-sensitivity C-reactive protein (hsCRP) levels were divided into three groups according to the hsCRP level: low (< 1 mg/L), average (1-3 mg/L), and high (> 3 mg/L), and the association of serum hsCRP level with BChE and albumin levels was investigated. We compared intercept values (y value at x = 0) of the regression formula obtained from repeated measurements between patients on dialysis and those with a known hereditary heterozygous BChE deficiency. Serum BChE and albumin levels in patients on dialysis were significantly lower, and a positive correlation was observed. The hsCRP level and the BChE and albumin levels were negatively correlated. BChE and albumin levels were highest in the low hsCRP group and lowest in the high hsCRP group, and a significant positive correlation was observed in all groups. The intercept values of the regression formula obtained from repeated measurements of BChE and albumin levels in patients on dialysis and a patient with hereditary heterozygous BChE deficiency were 0.383 and ---102.730, respectively, which may be useful in distinguishing hereditary causes.

The impact of hyperkalemia on mortality in cohort studies is difficult to assess because of fluctuations in serum potassium (S-K) levels, differences in the intensity of intervention for S-K, and the reliability of S-K levels measured across multiple facilities. Because our corporation has intervened for hyperkalemia when centrally measured S-K levels are ≥ 6.5 mEq/L, we investigated whether average S-K levels of 5.5–6.4 mEq/L were associated with higher mortality. This retrospective observational study included 678 patients undergoing dialysis who were divided into low (3.5–4.4 mEq/L), intermediate (4.5–5.4 mEq/L), and high (5.5–6.4 mEq/L) groups according to average S-K level, excluding those with levels ≥ 6.5 mEq/L at least once during the 3 months before the start of the study. The 2-year all-cause mortality was compared using a propensity score-matching (PSM) model with annually censoring of patients who had S-K levels of ≥ 6.5 mEq/L at least once after 10–12 months. Kaplan–Meier survival curves were compared using the log-rank test, after which Cox regression analysis was performed with adjustments. After PSM, S-K levels were 4.1 ± 0.2 mEq/L in the low group and 5.7 ± 0.2 in the high group (P < 0.001). Mortality was not significantly different between the two groups. After PSM, S-K levels were 4.9 ± 0.3 mEq/L in the intermediate group and 5.7 ± 0.2 in the high group (P < 0.001). Mortality was significantly lower in the high group compared with the intermediate group (hazard ratio 0.120, 95 https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000064682 .

Calcimimetics reduce mortality in older patients on dialysis. Because elderly patients are prone to protein-energy wasting (PEW) and inflammation, we investigated whether this effect is independent of these conditions. This retrospective study used propensity score matching to compare 2-year all-cause mortality between calcimimetic users and non-users. Patients were stratified into those without PEW and inflammation (Group 1, n = 240) and those with PEW and/or inflammation (Group 2, n = 498). Survival was assessed using Kaplan–Meier survival curves, censored for calcimimetic use and other covariates. In Group 2, mortality was significantly lower in calcimimetic users than in non-users after matching (hazard ratio [HR] 0.221, 95% confidence interval [CI] 0.073–0.670, P = 0.003, log-rank test), but not in Group 1. The significant difference in Group 2 was no longer observed after Cox proportional hazards regression adjusted for covariates that remained imbalanced following matching (adjusted HR, 0.272, 95% CI 0.073–1.006, P = 0.051). In Group 2, age-stratified analysis (median 69 years) showed significantly lower mortality in calcimimetic users among older patients (HR, 0.206, 95% CI, 0.058–0.728, P = 0.014), but not younger patients. These findings suggest that calcimimetics reduce mortality in elderly patients with PEW and/or inflammation, but not in those without these conditions.

Lower serum parathyroid hormone (PTH) levels are reported to improve mortality and fracture incidence in patients using calcimimetics. We investigated the prognosis of calcimimetic users and non-users with similar PTH levels within the target range. This retrospective study compared 2-year all-cause mortality and the incidence of any fracture in dialysis patients between calcimimetic users (n = 131) and non-users (n = 294) with PTH levels between 60 and 240 pg/mL using a propensity score-matched model. Kaplan-Meier survival curves censored by PTH level, calcimimetic use, and other factors were compared; then, adjusted Cox proportional hazards regression analysis was performed. After matching, mortality was significantly lower in calcimimetic users than in non-users (n = 130; hazard ratio [HR] 0.243, 95% confidence interval [CI] 0.073-0.801, P = 0.022, log-rank test). The PTH levels of users and non-users were 142.4 ± 49.4 and 132.7 ± 48.0 pg/mL, respectively (P = 0.127). Cox regression analysis demonstrated that mortality was significantly lower in users than in non-users (adjusted HR 0.260, 95% CI 0.071-0.947, P = 0.041). Calcimimetic use had no effect on fracture incidence. These findings suggest that, among dialysis patients with PTH levels between 60 and 240 pg/mL, mortality risk was significantly lower among calcimimetic users than in non-users. However, fracture risk was not significantly different between these groups.

Albumin leakage (Alb-L) and serum albumin (S-Alb) levels are predictors of mortality in dialysis patients. Because protein-energy wasting (PEW) and inflammation reduce hepatic albumin synthesis, we hypothesized that mortality would differ based on Alb-L and/or S-Alb levels, depending on the presence of PEW and inflammation. This retrospective study included 738 super high-flux hemodialysis (SHF HD) and online hemodiafiltration (OHDF) patients. Three-year all-cause mortality was compared in patients without PEW and inflammation (Group 1) and with PEW and/or inflammation (Group 2) using a propensity score matching model and Cox regression analysis with adjustment. In Group 2, mortality in patients with “high Alb-L” or “high S-Alb” was significantly lower in comparison to low groups, but not in Group 1. In Group 2, mortality in the “high Alb-L” and “high S-Alb (3.5 ± 0.2 g/dL)” group was lower than in other groups, including Group 1, except for the “high Alb-L” and “low S-Alb (3.2 ± 0.2 g/dL)” group, which had no deaths. In SHF HD and OHDF patients with PEW and/or inflammation, “high Alb-L” with normoalbuminemia to mild hypoalbuminemia improved survival to a level similar to patients without PEW and inflammation. Additionally, Alb-L and/or S-Alb had little impact on mortality in patients without PEW and inflammation.

Abstract Background When increasing the reduction ratio (RR) of α1-microglobulin (α1MG) to improve symptoms, the dialysis dose is usually increased. However, no studies on its effectiveness have been reported. Methods This cross-sectional study included 113 patients on predilution online hemodiafiltration (pre-OHDF) as of 1 July 2023. Univariate and multiple regression analyses were performed to investigate factors associated with the RR of α1MG. Results In univariate analysis, the RR of α1MG was significantly correlated with age, normalized protein catabolism rate (nPCR), membrane surface area, blood flow rate, ultrafiltration volume, and albumin leakage, but not with body mass index, albumin, C-reactive protein, substitution volume, transmembrane pressure, or Kt/V. In multiple regression analysis, the RR of α1MG remained significantly correlated with nPCR (P = 0.007) and albumin leakage (P < 0.001). Conclusions These findings suggest that in patients undergoing pre-OHDF with high protein intake, the use of high albumin leakage membranes rather than increasing the dialysis dose can significantly increase the RR of α1MG. Trial registration UMIN Clinical Trials Registry, UMIN000055718. Prospectively registered 3 October 2024. https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000063229

Although mortality is significantly lower with polyethersulfone (PES) membrane compared with polysulfone (PS) membrane in hemodialysis patients, no studies have investigated mortality in patients undergoing online hemodiafiltration (OHDF) according to the types of membrane materials. The retrospective observational study included 411 patients who were receiving OHDF with PES membrane (n = 190), PS membrane (n = 121), and asymmetric triacetate (ATA) membrane (n = 100) at our facilities on 1 July 2017. The 3-year all-cause mortality on PES membrane was compared with PS and ATA membranes using a propensity score matching model and Cox regression analysis with adjustments. The mortality was significantly lower in PES membrane compared with PS membrane (P = 0.012, log-rank test; hazard ratio 0.265, 95 https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000058078 and UMIN000051791 Registered 2 August 2023, Prospectively registered, https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000059102 .

Catheter exit-site infection is a major cause of withdrawal from peritoneal dialysis (PD). However, methods for caring for the peritoneal catheter and exit sites are not established and vary among facilities. No survey has been conducted on exit-site management in Japan. Here, we aimed to identify successful examples that led to best practices. The Japanese Society for Peritoneal Dialysis-led PD-related infection project was launched in 2023, under which a survey was conducted at 14 facilities nationwide that provide PD therapy. The survey content included questions about the timing of the initiation of exit-site care, the materials used in exit-site protection, and the disinfectants used for exit-site care. Seventy-one percent of the exit-site direction was downward. In all facilities, the exit site was dressed immediately after its creation for several days up to a certain period. Many facilities started exit-site care within 1–2 weeks of PD initiation. Notably, 50

BackgroundThe optimal timing for initiating dialysis and prognostic markers in chronic kidney disease (CKD) patients are under debate, with mortality and cardiovascular risks varying among patients. This study investigates whether the apoptosis inhibitor of macrophage (AIM), which is mostly bound to pentameric IgM, could serve as an effective indicator.MethodsWe prospectively followed 423 patients at dialysis initiation and 563 at various CKD stages. AIM dissociation from IgM and other serum components were measured in their serum samples. In vitro treatment of IgM-AIM complexes with their serum was conducted to assess AIM release from IgM. Survival analysis determined the associations of each variable with mortality and cardiovascular risk, and a cutoff value was calculated and validated using cross-validation.ResultsAIM dissociation from IgM increases with CKD progression and correlates with the serum uremic state, as shown by enhanced AIM release from IgM in vitro with sera from patients starting dialysis, but not those at earlier CKD stages. Patients at dialysis initiation with high proportion of serum IgM-free AIM (fAIM%) show elevated uremic toxins and other toxic metabolites, higher mortality, and increased cardiovascular risk compared to those with low fAIM%. This prognostic association is not seen with other CKD biomarkers, such as eGFR, creatinine, or inositol-phosphate. We determined the fAIM% cutoff of 46.27%, which predicts mortality two years post-dialysis initiation.ConclusionsThese findings suggest that the serum fAIM% could function as a prognostic marker at dialysis initiation and may have potential as a criterion for determining dialysis timing.

Background: The management of hypertriglyceridemia in patients with chronic kidney disease (CKD) is important. Pemafibrate, a novel selective peroxisome proliferator-activated receptor-alpha modulator with less toxic effects on liver and kidney function than those of other fibrates, has recently been approved for the treatment of patients with an estimated glomerular filtration rate (eGFR) lower than 30 mL/min/1.73 m2. However, the efficacy and safety of pemafibrate in patients with severe renal impairment have not yet been established. Methods: This single-center, retrospective observational study included 12 outpatients with CKD and hypertriglyceridemia, who were newly started on low-dose pemafibrate (0.1 mg/day) treatment between December 2021 and May 2023 and whose eGFRs were less than 30 mL/min/1.73 m2 at baseline. Blood samples were collected before and at 12 weeks after pemafibrate treatment. Results: After 12 weeks of treatment, the serum triglyceride level was significantly decreased, whereas the high-density lipoprotein cholesterol level was significantly increased. The serum alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transpeptidase, and uric acid levels were also significantly decreased, without worsening of the eGFR and serum creatinine levels. In the subgroup analysis, there were no significant differences in the changes in clinical parameters regardless of statin use and CKD stage at baseline. Conclusions: Low-dose pemafibrate administration in patients with severe renal impairment resulted in significant improvements in triglyceride, high-density lipoprotein cholesterol, and serum uric acid levels, and liver function, without adverse events.

A 61 -year -old asymptomatic female with autosomal dominant polycystic kidney disease (ADPKD) on tolvaptan therapy was hospitalized for acute kidney injury (AKI). Nephrolithiasis had already been diagnosed; however, the patient had not undergone any interventions. She also presented with hyponatremia possibly caused by overhydration. Because the estimated glomerular filtration rate (eGFR) decline was significantly higher than the predicted rate, we considered a possible case of postrenal AKI and examined computed tomography (CT), which revealed left hydronephrosis with a 9.4 -mm ureteric stone at the level of L3/L4. We restricted fluid intake, which resulted in an increase in sodium levels. She was treated with transurethral lithotripsy (TUL) twice, which successfully improved her kidney function. Although the serum sodium levels increase because of aquaresis in almost all patients treated with tolvaptan, our case was unique in that the patient presented with hyponatremia. We should pay more attention to the periodical follow-up of nephrolithiasis in addition to the increase in total kidney volume and decide the appropriate time to treat nephrolithiasis depending on the case. We should also keep in mind that ADPKD patients have a high frequency of nephrolithiasis and, even if asymptomatic, investigate urinary tract obstruction and hydronephrosis in case of AKI.

Background: Online hemodiafiltration (OHDF) has a lower mortality rate than hemodialysis (HD). We aimed to investigate the impact of the albumin leakage on the mortality of patients receiving HD or OHDF. Methods: In this single-center study, consecutive patients receiving renal replacement therapy between January and April 2018 were retrospectively registered. Using (1:1) propensity score matching, 3-year all-cause mortality was compared between patients receiving HD and OHDF, and the impact of albumin leakage on the mortality rate in both groups was investigated. Results: Of the 460 patients, 137 patients receiving HD were matched with an equal number of patients receiving OHDF. OHDF was associated with higher albumin leakage (p < 0.001) and a lower mortality than HD (log-rank test, p < 0.001). Albumin leakage was associated with mortality in patients receiving HD (per 1 g increase, hazard ratio (HR): 0.495, 95% confidence interval (CI): 0.275–0.888) and patients receiving OHDF (per 1 g increase, HR: 0.734, 95% CI: 0.588–0.915). Patients receiving HD, with the highest albumin leakage tertile (>3 g), had a similar mortality rate to patients receiving OHDF, with similar albumin leakage. Conclusions: The negative relationship between albumin leakage and mortality suggests the benefit of removing middle- to -large-molecular-weight substances to improve survival.

Serum levels of butyrylcholinesterase (BChE) are commonly used to assess liver function. Its levels have been reported to be significantly lower in patients undergoing dialysis. To the best of our knowledge, this is the first report of hereditary heterozygous BChE deficiency in a patient undergoing dialysis. Medical staff involved in the care of patients with BChE deficiency should be aware of anesthetic usage, because prolonged neuromuscular paralysis following the administration of succinylcholine or mivacurium may occur. However, in the heterozygotes, BChE activity is not completely absent. Therefore, differentiating patients undergoing dialysis is challenging. A 52-year-old man underwent living-related kidney transplantation for focal segmental glomerulosclerosis at 22 years of age. As the renal function gradually worsened, the patient began to receive combined hemodialysis and peritoneal dialysis therapy. No problems with anesthesia were observed in past surgeries. The patient’s BChE levels fluctuated between 76 and 170 U/L (reference range: 198-495 U/L); however, they had never been previously investigated. We suspected hereditary heterozygous BChE deficiency because the patient’s sister was also diagnosed with it. DNA sequencing revealed a heterozygous missense mutation (Gly365Arg) and a K-variant (Ala539Thr). Patients on dialysis with low serum BChE levels often present with low albumin levels which may be overlooked as malnutrition. Thus, BChE deficiency should be suspected in patients on dialysis with unexplained low serum BChE levels. In the case of heterozygous BChE deficiency, the reference value is low, and continuous monitoring is crucial.

It has been reported that survival on mild hypoalbuminemia due to high albumin leakage did not worsen in patients on hemodialysis (HD) or online hemodiafiltration (OHDF) even though the level of serum albumin is a classic nutrition marker associated with mortality. Survival was also equivalent on HD and OHDF for patients with similar levels of albumin leakage and serum albumin. Furthermore, survival on HD using a super high-flux (SHF) albumin-leaking membrane was better than that on HD using a SHF membrane, and survival on SHF albumin-leaking HD with high albumin leakage was better than that on OHDF with low albumin leakage. The following hypothesis regarding crosstalk between α1-microglobulin (α1MG) and albumin is proposed that can explain the mechanism by which the level of serum human mercaptoalbumin (HMA) increases postdialysis and decreases predialysis. At initiation of and during dialysis, the production of free α1MG in the liver increases by upregulation of the α1MG-bikunin precursor gene. The free α1MG rapidly reacts with some substances that are reversibly bound to human nonmercaptoalbumin (HNA)-1, resulting in the conversion to HMA and free α1MG with reduced activity (i.e., free α1MG with reduced or no antioxidant capacity) during dialysis and in the increased serum HMA level postdialysis. In addition, it is possible that both hypoalbuminemia and the conversion of HNA-1 to HMA increase the free form of indoxyl sulfate, which is removed by diffusion. The antioxidant capacity in serum after dialysis is mainly due to the very large amount of HMA, resulting in the conversion to HNA and the decreased serum HMA level before dialysis. However, the very small amount of free α1MG produced in the liver has strong antioxidant activity after dialysis.

INTRODUCTION:Recent advances in dialysis therapy have made it possible to remove middle molecules. Removal of small-middle molecules, such as β2-microglobulin, can now be achieved with conventional hemodialysis (HD), and removal of large-middle molecules has become a target, particularly for α1-microglobulin (AMG, 33 kD). The AMG reduction rate has emerged as a target for improvement of various clinical symptoms, but the effects on prognosis have yet to be determined. The "Japanese study of the effects of AMG (α1-microglobulin) reduction rates on survival" (JAMREDS) was started in April 2020, with the goal of determining if the AMG reduction rate associates with the risk of mortality and cardiovascular disease (CVD) events.METHODS:JAMREDS is a prospective observational study in patients on HD to examine the effects of: (1) AMG reduction rate on survival outcome and CVD events; (2) dialysis treatment modalities (HD, intermittent infusion hemodiafiltration(iHDF), pre/post-dilution online HDF) on survival and CVD events (based on AMG reduction rates with treatment mode); and (3) AMG reduction rates on survival and CVD events in patients undergoing each therapy (iHDF, pre/post-dilution online HDF). The number of planned subjects was 4,000 in preplanning. Data are collected using RED-Cap, which is an EDC system. A total of 9,930 patients were enrolled at the beginning of the study at 59 registered facilities. The JAMREDS observation period will continue until the end of 2023, after which the data will be cleaned and confirmed before analysis.CONCLUSION:This study may provide new evidence for the relationship between the amount of removed large-middle molecules (such as AMG) and the mortality and CVD risk. Comparisons with convection volumes will also be of interest.

Abstract Background No studies have compared mortality between acetate-containing bicarbonate dialysate (ABD) and acetate-free bicarbonate dialysate containing citrate (AFD) in hemodialysis (HD) or online hemodiafiltration (OHDF). We therefore compared mortality between ABD and AFD in each modality. Methods This retrospective observational study included 738 patients who were receiving super high-flux (SHF) or SHF albumin-leaking HD (n = 310: ABD 235 and AFD 75) or OHDF (n = 428: ABD 321 and AFD 107) at our institution between 1 April and 1 July 2017. Three-year all-cause mortality was compared between ABD and AFD in the HD or OHDF groups using a propensity score matching model. Kaplan–Meier survival curves were compared using the log-rank test, and then Cox regression analysis with adjustments was performed for some covariates that remained significant. Results After propensity score matching, mortality on ABD was not significantly different from that on AFD in the HD group [n = 75; hazard ratio (HR) 2.271, 95% confidence interval (CI) 0.863–5.981, P = 0.087] or in the OHDF group (n = 107; HR 1.944, 95% CI 0.585–6.458, P = 0.269) without adjustments. However, with adjustments using some covariates, mortality was significantly higher on ABD than on AFD (adjusted HR 4.501, 95% CI 1.434–14.125, P = 0.010) in the HD group, but not in the OHDF group. Conclusions These findings suggest that ABD worsens mortality more than AFD in patients on SHF and SHF albumin-leaking HD. Trial registration: UMIN Clinical Trials Registry, UMIN000053090. Prospectively registered 13 December 2023, https://center6.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000060581 .

Effects of the initial peritoneal dialysis (PD) prescription on clinical outcomes are unknown in Japan. We conducted a cohort study using data from Peritoneal Dialysis Outcomes and Practice Patterns Study. The patients were divided into two groups by the volume of the initial PD prescription (<= 4 L/day or > 4 L/day). Cause-specific Cox proportional hazards survival models were used to model the association between different PD prescriptions and the clinical outcomes. The outcomes included transfer to HD, mortality, the composite of mortality and transfer to HD, peritonitis, hospitalization, and the patient-reported outcomes (PROs). Of the 342 patients, 98 were prescribed <= 4 L/day, and 244 were prescribed > 4 L/day. Patients prescribed <= 4 L/day were older with a lower percentage being male, had more cardiovascular and cerebrovascular disease but lower diabetes prevalence, were more likely to be receiving CAPD, used more assisted PD, and had lower BMI and mean serum creatinine levels. There were no significant differences between groups in terms of transfer to HD, mortality, transfer to HD or mortality, hospitalization, incidence of peritonitis, and PROs. Patients with initial PD prescriptions of <= 4 L/day compared to > 4 L/day had similar clinical outcomes. This practice may provide health economic benefits in Japan.