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.

Association of Four Types of Vascular Access Including Arterial Superficialization with Mortality in Maintenance Hemodialysis Patients: A Nationwide Cohort Study in Japan.

INTRODUCTION: Vascular access usage varies widely across countries. Previous studies have evaluated the association of clinical outcomes with the three types of vascular access, namely, arteriovenous fistula (AVF), arteriovenous graft (AVG), and tunneled and cuffed central venous catheter (TC-CVC). However, little is known regarding the association between arterial superficialization (AS) and the mortality of patients. METHODS: A nationwide cohort study was conducted using data from the Japanese Society for Dialysis Therapy Renal Data Registry (2006-2007). We included patients aged ≥20 years undergoing hemodialysis with a dialysis vintage ≥6 months. The exposures of interest were the four types of vascular access: AVF, AVG, AS, and TC-CVC. Cox proportional hazard models were used to evaluate the associations of vascular access types with 1-year all-cause and cause-specific mortality. RESULTS: A total of 183,490 maintenance hemodialysis patients were included: 90.7% with AVF, 6.9% with AVG, 2.0% with AS, and 0.4% with TC-CVC. During the 1-year follow-up period, 13,798 patients died. Compared to patients with AVF, those with AVG, AS, and TC-CVC had a significantly higher risk of all-cause mortality after adjustment for confounding factors: adjusted hazard ratios (95% confidence intervals) - 1.30 (1.20-1.41), 1.56 (1.39-1.76), and 2.15 (1.77-2.61), respectively. Similar results were obtained for infection-related and cardiovascular mortality. CONCLUSION: This nationwide cohort study conducted in Japan suggested that AVF usage may have the lowest risk of all-cause mortality. The study also suggested that the usage of AS may be associated with better survival rates compared to those of TC-CVC in patients who are not suitable for AVF or AVG.

Patient-Centered Care Could Improve Quality of Life and Survival of Dialysis Patients: Dialysis Prescription and Daily Practice.

We now face a paradigm shift in clinical practice and research of dialysis from evidence-based medicine outcomes to patient-reported outcomes (PROs). It is imperative to establish a daily practice pattern based on the PROs, namely "patient-centered dialysis care." In 2005, we introduced the concept of "patient-oriented dialysis," which includes two fundamental components; adjustment of the dialysis prescription according to the PROs and nutritional intervention based on the global nutritional assessment. Routine examinations and team meetings were held to monitor the status of PROs and nutrition, and intervention plans were reevaluated. We found that the total score of the PROs was closely related to the survival rate of dialysis patients, and some of those were identified as independent mortality risk factors. These results might have shown that patient-centered dialysis care may improve the quality of life and the survival rate of dialysis patients. Polymethyl methacrylate (PMMA) is a unique synthetic membrane for a dialyzer with protein adsorption property and biocompatibility. Several clinical advantages of PMMA were reported as ameliorating inflammatory status, nutritional status, skin itchiness, and dialysis-related fatigue. PMMA is a fundamental and major choice for improving PROs in patient-centered dialysis care.

Comparable outcomes between a combination of peritoneal dialysis with once-weekly haemodialysis and thrice-weekly haemodialysis: a prospective cohort study.

BACKGROUND: Outcomes of a combination of peritoneal dialysis (PD) and once-weekly haemodialysis (PD + HD) have not been extensively studied. METHODS: This prospective cohort study using the Japanese Society for Dialysis Therapy Renal Data Registry included those who transitioned from PD to PD + HD therapy or thrice-weekly HD from 2011 to 2018. Exposure was PD + HD therapy compared with thrice-weekly HD. The outcome was time to all-cause or cause-specific death. Associations between PD + HD therapy and outcomes were examined by Cox regression. Sensitivity analyses were performed by propensity score (PS) matching, PS matching with a shared frailty model in which dialysis facilities were treated as a random effect, inverse probability weighting (IPW), PS adjustment, PS stratification, competing risk regression and on-treatment analyses in which data were censored at the transition to thrice-weekly HD for those on PD + HD therapy. RESULTS: During the study period, 1001 subjects transitioned to PD + HD therapy and 2031 to thrice-weekly HD. During a median follow-up of 3.5 years, 575 subjects died. All-cause, cardiovascular, congestive heart failure-related or infection-related mortality were not significantly different between those on PD + HD and those on thrice-weekly HD [hazard ratio 0.95 (95% confidence interval 0.78-1.16), 1.26 (0.92-1.72), 1.24 (0.77-1.99) and 0.89 (0.57-1.39), respectively]. Sensitivity analyses yielded similar results except that PD + HD therapy was associated with significantly lower all-cause mortality by PS adjustment and PS matching with the shared frailty model and lower infection-related mortality by PS adjustment and IPW. CONCLUSIONS: PD + HD therapy was associated with similar or potentially lower mortality compared with thrice-weekly HD. Considering a flexible lifestyle, PD + HD therapy could be a great option.

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.

Performance Status Modifies the Association Between Vitamin D Receptor Activator and Mortality or Fracture: A Prospective Cohort Study on the Japanese Society for Dialysis Therapy (JSDT) Renal Data Registry.

Immobilization osteoporosis is characterized by excess bone resorption. Vitamin D receptor activators (VDRA) might have adverse effects in immobilized patients. The objective of this study was to elucidate the impact of performance status (PS) on the associations between VDRA use and outcomes among hemodialysis patients. This is a prospective cohort study. Adults on hemodialysis in the Japanese Society for Dialysis Therapy (JSDT) Renal Data Registry were included. Exposure of interest was the use of VDRA. Outcomes were all-cause mortality and hip fracture. Associations between VDRA use and mortality or hip fractures were examined by Cox and Poisson regression analyses, respectively. Among 208,512 subjects, 128,535 were on VDRA. Poor PS was associated with higher calcium (Ca), lower parathyroid hormone, and higher alkaline phosphatase levels. The association between higher Ca levels and VDRA use was stronger among those with poor PS (p interaction 0.007). Adjusted hazard ratio (HR) (95% confidence interval [CI]) for mortality and incidence rate ratio (IRR) for hip fracture was 1.02 (95% CI, 0.99-1.05) and 0.93 (0.86-1.00) among users of VDRA, respectively. The VDRA use was associated with lower mortality and incidence of hip fractures among subjects with good PS but not among subjects with poor PS (p interaction 0.03 and 0.05). Effect modification by PS was observed for cardiovascular (CV) mortality but not for non-CV mortality. In conclusion, VDRA use was associated with better outcomes only among those with good PS. These results suggest that bone and mineral disorders among hemodialysis patients should be treated differently, depending on their performance status. © 2022 American Society for Bone and Mineral Research (ASBMR).

Parathyroidectomy vs Cinacalcet Among Patients Undergoing Hemodialysis.

CONTEXT: Parathyroidectomy (PTx) and cinacalcet are both effective treatments for secondary hyperparathyroidism in hemodialysis patients, but limited data exist comparing the long-term outcomes of these interventions. OBJECTIVE: We aimed to compare the risk of mortality among hemodialysis patients who underwent PTx and those who started treatment with cinacalcet. METHODS: In this prospective cohort study, comprising patients from the Japanese Society for Dialysis Therapy Renal Data Registry, patients who had intact parathyroid hormone (PTH) levels ≥ 300 pg/mL in late 2007 and underwent PTx or started treatment with cinacalcet in 2008 to 2009 were matched by propensity score at 1:3. PTx and cinacalcet were compared for all-cause mortality within 6 years. RESULTS: Among eligible patients, 894 patients who underwent PTx were matched with 2682 patients who started treatment with cinacalcet. The median baseline intact PTH levels were 588 pg/mL and 566 pg/mL in the PTx and cinacalcet groups, respectively. PTx resulted in greater reductions in intact PTH, calcium, and phosphorus levels compared with cinacalcet. During the 6-year follow-up period, 201 patients (22.5%) in the PTx group and 736 patients (27.4%) in the cinacalcet group died. PTx was associated with a lower risk of mortality compared with cinacalcet (hazard ratio, 0.78 [95% CI, 0.67-0.91]; P = 0.002). This association was more pronounced in patients with intact PTH levels ≥ 500 pg/mL and in patients with serum calcium levels ≥ 10.0 mg/dL (both P for interaction < 0.001). CONCLUSION: PTx compared with cinacalcet is associated with a lower risk of mortality, particularly among patients with severe secondary hyperparathyroidism.

Super high-flux membrane dialyzers improve mortality in patients on hemodialysis: a 3-year nationwide cohort study.

INTRODUCTION: In Japan, dialyzers are classified based on ß2-microglobulin clearance. Type I dialyzers are classified as low-flux dialyzers (<10 mL/min clearance), type II and III as high-flux dialyzers (≥10 to <30 mL/min and ≥30 to <50 mL/min clearance, respectively), and type IV and V as super high-flux dialyzers (≥50 to <70 mL/min and ≥70 mL/min clearance, respectively). Super high-flux dialyzers are commonly used, but their superiority over low-flux dialyzers is controversial. METHODS: In this nationwide prospective cohort study, we analyzed Japanese Society for Dialysis Therapy Renal Data Registry data collected at the end of 2008 and 2011. We enrolled 242,467 patients on maintenance hemodialysis and divided them into five groups by dialyzer type. We assessed the associations of each dialyzer type with 3-year all-cause mortality using Cox proportional hazards models and performed propensity score matching analysis, adjusting for potential confounders. RESULTS: By the end of 2011, 53,172 (21.9%) prevalent dialysis patients had died. Mortality significantly decreased according to dialyzer type. Hazard ratios (HRs) were significantly higher for type I, II and III compared with type IV (reference) after adjustment for basic factors and further adjustment for dialysis-related factors. HR was significantly higher for type I, but significantly lower for type V, after further adjustment for nutrition- and inflammation-related factors. These significant findings were also evident after propensity score matching. CONCLUSIONS: Hemodialysis using super high-flux dialyzers might reduce mortality. Randomized controlled trials are warranted to clarify whether these type V dialyzers can improve prognosis.

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.

Clinical impact of patient-centered care for hemodialysis patients using routine assessment of symptom burden.

The study aimed to verify the impact of our clinical strategy, which emphasizes patient-centered care, based on patient-reported outcome measures (PROMs) results in hemodialysis patients. We developed our original PROM (comprising 20 items) to assess patients' symptom burden. To confirm the validity of our clinical pattern, we performed various analyses using PROM data. We retrospectively enrolled 383 individuals (mean age 66.3 years; 252 men), collected their PROM data in December 2013, and followed them up for 3 years. We noted a lower mortality rate and a lower prevalence of itching in our facilities than in previous surveys and reports in Japan. Furthermore, we observed that the severity of symptom burden affected medium-term prognosis. This is the first study to report the results of patient-centered medical practice utilizing PROMs in dialysis care. Careful attention should be paid to patients' symptom burden, as performed in objective data management.

Association between the use of exchange devices for peritoneal dialysis fluids and peritonitis incidence: A nationwide cohort study.

BACKGROUND: The use of exchange devices for peritoneal dialysis (PD) fluids is a common practice in Japan. Evidence on the effectiveness of exchange devices in preventing PD-related peritonitis is scarce. We evaluated the association between the use of exchange devices for PD fluids and peritonitis incidence. METHODS: We retrospectively enrolled 3845 patients, aged ≥20 years, receiving PD for ≥3 months, with available data on the exchange procedure for PD fluids and peritonitis incidence that was obtained from the Japan Renal Data Registry, a nationwide annual survey. The patients were grouped according to whether the manual or device PD fluid exchange method was used. The onset of peritonitis was defined as a leukocyte count of >100/µL (neutrophils ≥50%) in PD effluents. We applied quasi-Poisson regression analyses to estimate the incidence rate ratio (IRR). Age, sex, PD vintage, body mass index, automated PD use, residual kidney function, comorbidities, haemoglobin and serum albumin were adjusted as potential confounders. RESULTS: Older age, automated PD use, diabetes as comorbidity and lower haemoglobin levels were associated with the use of exchange devices for PD fluids. Patients using devices for PD fluid exchange (69.2%) had an increased risk of peritonitis of 37% (IRR: 1.37, 95% confidence interval (CI): 1.07-1.75) and 28% (IRR: 1.28, 95% CI: 1.00-1.63) in the crude and multivariate adjustment models, respectively. CONCLUSIONS: The use of exchange devices for PD fluids and peritonitis incidence showed no favourable association. There may remain possible residual confounding by indication.

Dialyzer surface area is a significant predictor of mortality in patients on hemodialysis: a 3-year nationwide cohort study.

A target Kt/V of > 1.4 and use of a high-flux dialyzer are recommended for patients on hemodialysis. However, there is little information on the relationship between the dialyzer surface area and mortality in these patients. In this nationwide cohort study, we aimed to clarify this relationship by analyzing data from the Japanese Society for Dialysis Therapy for 2010-2013. We enrolled 234,638 patients on hemodialysis who were divided according to quartile for dialyzer surface area into the S group (small, < 1.5 m2), M group (medium, 1.5 m2), L group (large, 1.6 to < 2.0 m2), or XL group (extra-large, ≥ 2.0 m2). We assessed the association of each group with 3-year mortality using Cox proportional hazards models and performed propensity score matching analysis. By the end of 2013, a total of 53,836 patients on dialysis (22.9%) had died. There was a significant decrease in mortality with larger dialyzer surface areas. The hazard ratio (95% confidence interval) was significantly higher in the S group (1.15 [1.12-1.19], P < 0.0001) and significantly lower in the L group (0.89 [0.87-0.92] P < 0.0001) and XL group (0.75 [0.72-0.78], P < 0.0001) than in the M group as a reference after adjustment for all confounders. Findings were robust in several sensitivity analyses. Furthermore, the findings remained significant after propensity score matching. Hemodialysis using dialyzers, especially super high-flux dialyzers with a larger surface area might reduce mortality rates, and a surface area of ≥ 2.0 m2 is superior, even with the same Kt/V.

Dialyzer Classification and Mortality in Hemodialysis Patients: A 3-Year Nationwide Cohort Study.

Background: Dialyzers are classified as low-flux, high-flux, and protein-leaking membrane dialyzers internationally and as types I, II, III, IV, and V based on ß2-microglobulin clearance rate in Japan. Type I dialyzers correspond to low-flux membrane dialyzers, types II and III to high-flux membrane dialyzers, and types IV and V to protein-leaking membrane dialyzers. Here we aimed to clarify the association of dialyzer type with mortality. Methods: This nationwide retrospective cohort study analyzed data from the Japanese Society for Dialysis Therapy Renal Data Registry from 2010 to 2013. We enrolled 238,321 patients on hemodialysis who were divided into low-flux, high-flux, and protein-leaking groups in the international classification and into type I to V groups in the Japanese classification. We assessed the associations of each group with 3-year all-cause mortality using Cox proportional hazards models and performed propensity score matching analysis. Results: By the end of 2013, 55,308 prevalent dialysis patients (23.2%) had died. In the international classification subgroup analysis, the hazard ratio (95% confidence interval) was significantly higher in the low-flux group [1.12 (1.03-1.22), P = 0.009] and significantly lower in the protein-leaking group [0.95 (0.92-0.98), P = 0.006] compared with the high-flux group after adjustment for all confounders. In the Japanese classification subgroup analysis, the hazard ratios were significantly higher for types I [1.10 (1.02-1.19), P = 0.015] and II [1.10 (1.02-1.39), P = 0.014] but significantly lower for type V [0.91 (0.88-0.94), P < 0.0001] compared with type IV after adjustment for all confounders. These significant findings persisted after propensity score matching under both classifications. Conclusions: Hemodialysis using protein-leaking dialyzers might reduce mortality rates. Furthermore, type V dialyzers are superior to type IV dialyzers in hemodialysis patients.

Combination of once-weekly haemodialysis with peritoneal dialysis is associated with lower mortality compared with peritoneal dialysis alone: a longitudinal study.

BACKGROUND: Approximately 20% of patients on peritoneal dialysis (PD) in Japan are on combination with once-weekly haemodialysis (HD). This study aimed to compare outcomes of combination therapy and PD alone. METHODS: This longitudinal study on the Japanese Renal Data Registry included patients on PD from 2010 to 2014. Subjects were followed until the end of 2015. Exposure of interest was combination therapy compared with PD alone. Outcomes were complete transition to HD, all-cause mortality, cardiovascular (CV) mortality and congestive heart failure (CHF)-related mortality. Patients who initiated combination therapy were matched with those on PD alone by propensity scores. Data were analysed using Cox regression models. RESULTS: Among the matched cohort, 608 patients were on combination therapy and 869 were on PD alone. Decline in body weight and residual renal function was more prominent in the combination therapy group. During a median follow-up of 2.5 years, 224 deaths occurred. All-cause mortality {hazard ratio (HR) [95% confidence interval (CI)] 0.56 (0.42-0.75)}, CV mortality [HR 0.48 (0.32-0.72)] and CHF-related mortality [HR 0.19 (0.07-0.55)] were significantly lower, but complete transition to HD was significantly earlier [HR 1.72 (1.45-2.03)] in the combination therapy group. Sensitivity analyses considering the effects of dialysis facilities yielded similar results. Assuming causality, numbers needed to treat to prevent one death per year were 34 patients. CONCLUSIONS: Combination therapy was associated with lower all-cause mortality, CV mortality and CHF-related mortality, but earlier transition to HD compared with PD alone, which might be due to better fluid removal by HD.

High-performance dialyzers and mortality in maintenance hemodialysis patients.

Few data are available regarding the association of dialyzer type with prognosis. In Japan, dialyzers are classified as types I, II, III, IV, and V based on ß2-microglobulin clearance rates of < 10, < 30, < 50, < 70, and ≥ 70 mL/min, respectively. We investigated the relationship of the 5 dialyzer types with 1-year mortality. This nationwide cohort study used data collected at the end of 2008 and 2009 by the Japanese Society for Dialysis Therapy Renal Data Registry. We enrolled 203,008 patients on maintenance hemodialysis who underwent hemodialysis for at least 1 year and were managed with any of the 5 dialyzer types. To evaluate the association of dialyzer type with 1-year all-cause mortality, Cox proportional hazards models and propensity score-matched analyses were performed. After adjustment of the data with clinicodemographic factors, the type I, II, and III groups showed significantly higher hazard ratios (HRs) than the type IV dialyzers (reference). After adjustment for Kt/V and ß2-microglobulin levels, the HRs were significantly higher in the type I and II groups. After further adjustment for nutrition- and inflammation-related factors, the HRs were not significantly different between the type IV and type I and II groups. However, type V dialyzers consistently showed a significantly lower HR. With propensity score matching, the HR for the type V dialyzer group was significantly lower than that for the type IV dialyzer group. Additional long-term trials are required to determine whether type V dialyzers, which are high-performance dialyzers, can improve prognosis.

Encapsulating Peritoneal Sclerosis and Mortality Related to Infection in Patients on Combination Once-Weekly Hemodialysis with Peritoneal Dialysis.

INTRODUCTION: Previous studies showed that the combination of peritoneal dialysis (PD) and once-weekly hemodialysis is associated with lower all-cause and cardiovascular mortality. This study aimed to compare the incidence of encapsulating peritoneal sclerosis (EPS) and infection-related mortality among those on combination therapy and those on PD alone. METHODS: This prospective study on the Japanese Renal Data Registry included patients on PD from 2010 to 2014. Subjects were followed up until the end of 2015. Exposure of interest was combination therapy compared with PD alone. Patients who transitioned to combination therapy were matched with those on PD alone by propensity scores. Outcomes were EPS and infection-related mortality. Data were analyzed using Cox regression models. RESULTS: Among the matched cohort, 608 and 869 patients were on combination therapy and on PD alone, respectively. Dialysate-to-plasma creatinine (D/P Cr) ratio decreased over time among those on combination therapy, while the ratio increased among those on PD alone (p = 0.01 by the mixed-effects model). During a median follow-up of 2.5 years, 33 experienced EPS and 55 died of infection. Combination therapy was associated with lower infection-related mortality (HR [95% CI]: 0.52 [0.28-0.95]) but not with EPS (HR: 1.21 [0.61-2.40]). Lower mortality was not limited to intra-abdominal infection but also observed for pulmonary infection. Sensitivity analyses considering the effects of dialysis facilities yielded similar results. CONCLUSIONS: Combination therapy was associated with lower infection-related mortality. It was also associated with a decline in the D/P Cr ratio over time but not with lower incidence of EPS during the short observation period.

Pre-dialysis Hyponatremia and Change in Serum Sodium Concentration During a Dialysis Session Are Significant Predictors of Mortality in Patients Undergoing Hemodialysis.

BACKGROUND: Previous studies have shown that hyponatremia is associated with greater mortality in hemodialysis (HD) patients. However, there have been few reports regarding the importance of the change in serum sodium (SNa) concentration (ΔSNa) during dialysis sessions. To investigate the relationships of pre-dialysis hyponatremia and ΔSNa during a dialysis session with mortality, we analyzed data from a national registry of Japanese patients with end-stage kidney disease. METHODS: We identified 178,114 patients in the database who were undergoing HD 3 times weekly. The study outcome was 2-year all-cause mortality, and the baseline SNa concentrations were categorized into quintiles. We evaluated the relationships of SNa concentration and ΔSNa with mortality using Cox proportional hazards models. RESULTS: During a 2-year follow-up period, 25,928 patients died. Each 1-mEq/l reduction in pre-HD SNa concentration was associated with a cumulatively greater risk of all-cause mortality (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.05-1.06). In contrast, a larger ΔSNa was associated with higher all-cause mortality (HR for a 1-mEq/l increase in ΔSNa, 1.02; 95% CI 1.01-1.02). The combination of low pre-HD SNa concentration and large ΔSNa was also associated with higher mortality (HR 1.09; 95% CI 1.05-1.13). Participants with the lowest SNa concentration (≤136 mEq/L) and the highest ΔSNa (>4 mEq/L) showed higher mortality than those with an intermediate pre-HD SNa concentration (137-140 mEq/L) and the lowest ΔSNa (≤2 mEq/L). CONCLUSIONS: Lower pre-HD SNa concentration and higher ΔSNa are associated with a greater risk of mortality in patients undergoing HD.

Association between anemia and mortality in hemodialysis patients is modified by the presence of diabetes.

BACKGROUND: The prevalence and severity of anemia differ between diabetic and non-diabetic patients. We investigated whether the effect of hemoglobin (Hb) on patient outcome was affected by the presence or absence of diabetes among Japanese patients receiving chronic hemodialysis (HD). METHODS: We enrolled 149,308 patients from a nationwide dialysis registry in Japan at the end of 2012 (mean age, 67.6 ± 12.3 years; male, 61.7%; diabetes, 43.5%; median dialysis duration, 65 months) who underwent three HD sessions weekly. One-year all-cause and cardiovascular (CV) mortality were assessed using Cox regression analysis and competing-risks regression analysis. We used multiple imputation to deal with missing covariate data. RESULTS: Baseline Hb and serum ferritin levels were independently associated with all-cause and CV mortality. In non-diabetic patients, a significantly higher risk for all-cause mortality compared to the reference group (10 to 11 g/dL) was observed in patients with Hb < 8 g/dL (hazard ratio (HR): 1.266; 95% confidence interval (CI) 1.097-1.460) and 8 to 9 g/dL(HR: 1.153; 95% CI 1.030-1.290). On the other hand, diabetic HD patients in the same Hb category group did not have increased risk of all-cause mortality. CONCLUSIONS: We found that non-diabetic HD patients had an increased risk of all-cause mortality if they had lower Hb levels, whereas the effect of Hb levels on mortality was attenuated in diabetic HD patients. These data suggest that the association between Hb levels and mortality rate could be different between diabetic and non-diabetic HD patients.

Association of kidney transplantation with mortality on hemodialysis after graft failure.

BACKGROUND: Although a substantial number of patients return to dialysis after kidney transplant failure, it remains controversial whether transplant-failure patients have a higher mortality risk than transplant-naïve patients on dialysis who have never undergone kidney transplantation. We compared outcomes of transplant-failure and transplant-naïve patients on hemodialysis. METHODS: Data from the Japanese National Dialysis Registry (2012-2013) were analyzed, including 220,438 prevalent hemodialysis patients. Multivariable Cox models were used to compare all-cause, cardiovascular, and infection-related mortality during 1-year follow-up between transplant-failure and transplant-naïve patients. Multiple imputation and propensity score matching were utilized as sensitivity analyses. RESULTS: During 209,377 patient-years of follow-up, 18,648 all-cause deaths (8.5% of all patients), 7700 cardiovascular deaths (41% of all-cause deaths), and 3806 infection-related deaths (20% of all-cause deaths) were observed. Adjusted hazard ratios [95% confidence intervals] for all-cause, cardiovascular, and infection-related deaths among transplant-failure patients were 0.81 [0.59-1.11], 0.54 [0.30-0.98], and 1.54 [0.92-2.59], respectively. Sensitivity analyses using multiple imputation and propensity score matching yielded similar results. CONCLUSIONS: This Japanese cohort study suggested that a cardiovascular mortality risk of transplant-failure patients could be significantly lower than that of transplant-naïve patients, while there might be a trend toward a higher infection-related mortality risk in transplant-failure patients. However, this retrospective, single-country study can introduce an immortal time bias in transplant-failure patients, and limit the external validity. Further prospective studies are warranted to improve the comparability of outcomes between transplant-failure and transplant-naïve patients, and to examine worldwide the generalizability of the potential cardiovascular benefit of kidney transplantation even after returning to dialysis.