Effect of Dialysate and Plasma Sodium on Mortality in a Global Historical Hemodialysis Cohort.

SIGNIFICANCE STATEMENT: This large observational cohort study aimed to investigate the relationship between dialysate and plasma sodium concentrations and mortality among maintenance hemodialysis patients. Using a large multinational cohort of 68,196 patients, we found that lower dialysate sodium concentrations (≤138 mmol/L) were independently associated with higher mortality compared with higher dialysate sodium concentrations (>138 mmol/L). The risk of death was lower among patients exposed to higher dialysate sodium concentrations, regardless of plasma sodium levels. These results challenge the prevailing assumption that lower dialysate sodium concentrations improve outcomes in hemodialysis patients. The study confirms that until robust evidence from randomized trials that are underway is available, nephrologists should remain cautious in reconsideration of dialysate sodium prescribing practices to optimize cardiovascular outcomes and reduce mortality in this population. BACKGROUND: Excess mortality in hemodialysis (HD) patients is largely due to cardiovascular disease and is associated with abnormal fluid status and plasma sodium concentrations. Ultrafiltration facilitates the removal of fluid and sodium, whereas diffusive exchange of sodium plays a pivotal role in sodium removal and tonicity adjustment. Lower dialysate sodium may increase sodium removal at the expense of hypotonicity, reduced blood volume refilling, and intradialytic hypotension risk. Higher dialysate sodium preserves blood volume and hemodynamic stability but reduces sodium removal. In this retrospective cohort, we aimed to assess whether prescribing a dialysate sodium ≤138 mmol/L has an effect on survival outcomes compared with dialysate sodium >138 mmol/L after adjusting for plasma sodium concentration. METHODS: The study population included incident HD patients from 875 Fresenius Medical Care Nephrocare clinics in 25 countries between 2010 and 2019. Baseline dialysate sodium (≤138 or >138 mmol/L) and plasma sodium (<135, 135-142, >142 mmol/L) concentrations defined exposure status. We used multivariable Cox regression model stratified by country to model the association between time-varying dialysate and plasma sodium exposure and all-cause mortality, adjusted for demographic and treatment variables, including bioimpedance measures of fluid status. RESULTS: In 2,123,957 patient-months from 68,196 incident HD patients with on average three HD sessions per week dialysate sodium of 138 mmol/L was prescribed in 63.2%, 139 mmol/L in 15.8%, 140 mmol/L in 20.7%, and other concentrations in 0.4% of patients. Most clinical centers (78.6%) used a standardized concentration. During a median follow-up of 40 months, one third of patients ( n =21,644) died. Dialysate sodium ≤138 mmol/L was associated with higher mortality (multivariate hazard ratio for the total population (1.57, 95% confidence interval, 1.25 to 1.98), adjusted for plasma sodium concentrations and other confounding variables. Subgroup analysis did not show any evidence of effect modification by plasma sodium concentrations or other patient-specific variables. CONCLUSIONS: These observational findings stress the need for randomized evidence to reliably define optimal standard dialysate sodium prescribing practices.

Low dialysate sodium levels for chronic haemodialysis.

BACKGROUND: Cardiovascular (CV) disease is the leading cause of death in dialysis patients and is strongly associated with fluid overload and hypertension. It is plausible that low dialysate sodium ion concentration [Na+] may decrease total body sodium content, thereby reducing fluid overload and hypertension and ultimately reducing CV morbidity and death. This is an update of a review first published in 2019. OBJECTIVES: This review evaluated the harms and benefits of using a low (< 138 mM) dialysate [Na+] for maintenance haemodialysis (HD) patients. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 1 October 2024 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs), both parallel and cross-over, of low (< 138 mM) versus neutral (138 to 140 mM) or high (> 140 mM) dialysate [Na+] for maintenance HD patients were included. DATA COLLECTION AND ANALYSIS: Two authors independently screened studies for inclusion and extracted data. Statistical analyses were performed using the random-effects model, and results expressed as risk ratios (RR) for dichotomous outcomes, and mean differences (MD) or standardised MD (SMD) for continuous outcomes, with 95% confidence intervals (CI). Confidence in the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). MAIN RESULTS: We included 17 studies randomising 509 patients, with data available for 452 patients after dropouts. All but three studies evaluated a fixed concentration of low dialysate [Na+], with one using profiled dialysate [Na+] and two using individualised dialysate [Na+]. Five were parallel group studies, and 12 were cross-over studies. Of the latter, only six used a washout between intervention and control periods. Most studies were short-term with a median (interquartile range) follow-up of 4 (4 to 16) weeks. Two were of a single HD session and two of a single week's HD. Seven studies were conducted prior to 2000, and six reported the use of obsolete HD practices. Other than for indirectness arising from older studies, risks of bias in the included studies were generally low. Compared to neutral or high dialysate [Na+] (≥ 138 mM), low dialysate [Na+] (< 138 mM) reduces interdialytic weight gain (14 studies, 515 participants: MD -0.36 kg, 95% CI -0.50 to -0.22; high certainty evidence) and antihypertensive medication use (5 studies, 241 participants: SMD -0.37, 95% CI -0.64 to -0.1; high certainty evidence), and probably reduces left ventricular mass index (2 studies, 143 participants: MD -7.65 g/m2, 95% CI -14.48 to -0.83; moderate certainty evidence), predialysis mean arterial pressure (MAP) (5 studies, 232 participants: MD -3.39 mm Hg, 95% CI -5.17 to -1.61; moderate certainty evidence), postdialysis MAP (5 studies, 226 participants: MD -3.17 mm Hg, 95% CI -4.68 to 1.67; moderate certainty evidence), predialysis serum [Na+] (11 studies, 435 participants: MD -1.26 mM, 95% CI -1.81 to -0.72; moderate certainty evidence) and postdialysis serum [Na+] (6 studies, 188 participants: MD -3.09 mM, 95% CI -4.29 to -1.88; moderate certainty evidence). Compared to neutral or high dialysate [Na+], low dialysate [Na+] probably increases intradialytic hypotension events (13 studies, 15,764 HD sessions: RR 1.58, 95% 1.25 to 2.01; moderate certainty evidence) and intradialytic cramps (10 studies, 14,559 HD sessions: RR 1.84, 95% 1.29 to 2.64; moderate certainty evidence). Effect size for important outcomes were generally greater with low dialysate [Na+] compared to high compared with neutral dialysate [Na+], although formal hypothesis testing identifies that the difference was only certain for postdialysis serum [Na+]. Compared to neutral or high dialysate [Na+], it is uncertain whether low dialysate [Na+] affects intradialytic or interdialytic MAP, and dietary salt intake. It is also uncertain whether low dialysate [Na+] changed extracellular fluid status, venous tone, arterial vascular resistance, left ventricular volumes, or fatigue. Studies did not examine CV or all-cause death, CV events, or hospitalisation. AUTHORS' CONCLUSIONS: Low dialysate [Na+] reduces intradialytic weight gain and probably blood pressure, which are effects directionally associated with improved outcomes. However, the intervention probably increases intradialytic hypotension and probably reduces serum [Na+], effects that are associated with an increased risk of death. The effect of the intervention on overall patient health and well-being is unknown. Further evidence is needed in the form of longer-term studies in contemporary settings, evaluating end-organ effects in small-scale mechanistic studies using optimal methods, and clinical outcomes in large-scale multicentre RCTs.

Home Versus Facility Dialysis and Mortality in Australia and New Zealand.

RATIONALE & OBJECTIVE: Mortality is an important outcome for all dialysis stakeholders. We examined associations between dialysis modality and mortality in the modern era. STUDY DESIGN: Observational study comparing dialysis inception cohorts 1998-2002, 2003-2007, 2008-2012, and 2013-2017. SETTING & PARTICIPANTS: Australia and New Zealand (ANZ) dialysis population. EXPOSURE: The primary exposure was dialysis modality: facility hemodialysis (HD), continuous ambulatory peritoneal dialysis (CAPD), automated PD (APD), or home HD. OUTCOME: The main outcome was death. ANALYTICAL METHODS: Cause-specific proportional hazards models with shared frailty and subdistribution proportional hazards (Fine and Gray) models, adjusting for available confounding covariates. RESULTS: In 52,097 patients, the overall death rate improved from ~15 deaths per 100 patient-years in 1998-2002 to ~11 in 2013-2017, with the largest cause-specific contribution from decreased infectious death. Relative to facility HD, mortality with CAPD and APD has improved over the years, with adjusted hazard ratios in 2013-2017 of 0.88 (95% CI, 0.78-0.99) and 0.91 (95% CI, 0.82-1.00), respectively. Increasingly, patients with lower clinical risk have been adopting APD, and to a lesser extent CAPD. Relative to facility HD, mortality with home HD was lower throughout the entire period of observation, despite increasing adoption by older patients and those with more comorbidities. All effects were generally insensitive to the modeling approach (initial vs time-varying modality, cause-specific versus subdistribution regression), different follow-up time intervals (5 year vs 7 year vs 10 year). There was no effect modification by diabetes, comorbidity, or sex. LIMITATIONS: Potential for residual confounding, limited generalizability. CONCLUSIONS: The survival of patients on PD in 2013-2017 appears greater than the survival for patients on facility HD in ANZ. Additional research is needed to assess whether changing clinical risk profiles over time, varied dialysis prescription, and morbidity from dialysis access contribute to these findings.

Relationship between measured and prescribed dialysate sodium in haemodialysis: a systematic review and meta-analysis.

BACKGROUND: Dialysate sodium (DNa) prescription policy differs between haemodialysis (HD) units, and the optimal DNa remains uncertain. We sought to summarize the evidence on the agreement between prescribed and delivered DNa, and whether the relationship varied according to prescribed DNa. METHODS: We searched MEDLINE and PubMed from inception to 26 February 2020 for studies reporting measured and prescribed DNa. We analysed results reported in aggregate with random-effects meta-analysis. We analysed results reported by individual sample, using mixed-effects Bland-Altman analysis and linear regression. Pre-specified subgroup analyses included method of sodium measurement, dialysis machine manufacturer and proportioning method. RESULTS: Seven studies, representing 908 dialysate samples from 10 HD facilities (range 16-133 samples), were identified. All but one were single-centre studies. Studies were of low to moderate quality. Overall, there was no statistically significant difference between measured and prescribed DNa {mean difference = 0.73 mmol/L [95% confidence interval (CI) -1.12 to 2.58; P = 0.44]} but variability across studies was substantial (I2 = 99.3%). Among individually reported samples (n = 295), measured DNa was higher than prescribed DNa by 1.96 mmol/L (95% CI 0.23-3.69) and the 95% limits of agreement ranged from -3.97 to 7.88 mmol/L. Regression analysis confirmed a strong relationship between prescribed and measured DNa, with a slope close to 1:1 (ß = 1.16, 95% CI 1.06-1.27; P < 0.0001). CONCLUSIONS: A limited number of studies suggest that, on average, prescribed and measured DNa are similar. However, between- and within-study differences were large. Further consideration of the precision of delivered DNa is required to inform rational prescribing.

Effect of Low-Sodium versus Conventional Sodium Dialysate on Left Ventricular Mass in Home and Self-Care Satellite Facility Hemodialysis Patients: A Randomized Clinical Trial.

BACKGROUND: Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality. There is a global trend to lower dialysate sodium with the goal of reducing fluid overload. METHODS: To investigate whether lower dialysate sodium during hemodialysis reduces left ventricular mass, we conducted a randomized trial in which patients received either low-sodium dialysate (135 mM) or conventional dialysate (140 mM) for 12 months. We included participants who were aged >18 years old, had a predialysis serum sodium ≥135 mM, and were receiving hemodialysis at home or a self-care satellite facility. Exclusion criteria included hemodialysis frequency >3.5 times per week and use of sodium profiling or hemodiafiltration. The main outcome was left ventricular mass index by cardiac magnetic resonance imaging. RESULTS: The 99 participants had a median age of 51 years old; 67 were men, 31 had diabetes mellitus, and 59 had left ventricular hypertrophy. Over 12 months of follow-up, relative to control, a dialysate sodium concentration of 135 mmol/L did not change the left ventricular mass index, despite significant reductions at 6 and 12 months in interdialytic weight gain, in extracellular fluid volume, and in plasma B-type natriuretic peptide concentration (ratio of intervention to control). The intervention increased intradialytic hypotension (odds ratio [OR], 7.5; 95% confidence interval [95% CI], 1.1 to 49.8 at 6 months and OR, 3.6; 95% CI, 0.5 to 28.8 at 12 months). Five participants in the intervention arm could not complete the trial because of hypotension. We found no effect on health-related quality of life measures, perceived thirst or xerostomia, or dietary sodium intake. CONCLUSIONS: Dialysate sodium of 135 mmol/L did not reduce left ventricular mass relative to control, despite improving fluid status. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: The Australian New Zealand Clinical Trials Registry, ACTRN12611000975998.

Icodextrin Versus Glucose Solutions for the Once-Daily Long Dwell in Peritoneal Dialysis: An Enriched Systematic Review and Meta-analysis of Randomized Controlled Trials.

RATIONALE & OBJECTIVE: The efficacy and safety of icodextrin versus glucose-only peritoneal dialysis (PD) regimens is unclear. The aim of this study was to compare once-daily long-dwell icodextrin versus glucose among patients with kidney failure undergoing PD. STUDY DESIGN: Systematic review of randomized controlled trials (RCTs), enriched with unpublished data from investigator-initiated and industry-sponsored studies. SETTING & STUDY POPULATIONS: Individuals with kidney failure receiving regular PD treatment enrolled in clinical trials of dialysate composition. SELECTION CRITERIA FOR STUDIES: Medline, Embase, CENTRAL, Ichushi Web, 10 Chinese databases, clinical trials registries, conference proceedings, and citation lists from inception to November 2018. Further data were obtained from principal investigators and industry clinical study reports. DATA EXTRACTION: 2 independent reviewers selected studies and extracted data using a prespecified extraction instrument. ANALYTIC APPROACH: Qualitative synthesis of demographics, measurement scales, and outcomes. Quantitative synthesis with Mantel-Haenszel risk ratios (RRs), Peto odds ratios (ORs), or (standardized) mean differences (MDs). Risk of bias of included studies at the outcome level was assessed using the Cochrane risk-of-bias tool for RCTs. RESULTS: 19 RCTs that enrolled 1,693 participants were meta-analyzed. Ultrafiltration was improved with icodextrin (medium-term MD, 208.92 [95% CI, 99.69-318.14] mL/24h; high certainty of evidence), reflected also by fewer episodes of fluid overload (RR, 0.43 [95% CI, 0.24-0.78]; high certainty). Icodextrin-containing PD probably decreased mortality risk compared to glucose-only PD (Peto OR, 0.49 [95% CI, 0.24-1.00]; moderate certainty). Despite evidence of lower peritoneal glucose absorption with icodextrin-containing PD (medium-term MD, -40.84 [95% CI, -48.09 to-33.59] g/long dwell; high certainty), this did not directly translate to changes in fasting plasma glucose (-0.50 [95% CI, -1.19 to 0.18] mmol/L; low certainty) and hemoglobin A1c levels (-0.14% [95% CI, -0.34% to 0.05%]; high certainty). Safety outcomes and residual kidney function were similar in both groups; health-related quality-of-life and pain scores were inconclusive. LIMITATIONS: Trial quality was variable. The follow-up period was heterogeneous, with a paucity of assessments over the long term. Mortality results are based on just 32 events and were not corroborated using time-to-event analysis of individual patient data. CONCLUSIONS: Icodextrin for once-daily long-dwell PD has clinical benefit for some patients, including those not meeting ultrafiltration targets and at risk for fluid overload. Future research into patient-centered outcomes and cost-effectiveness associated with icodextrin is needed.

Haemodialysis withdrawal in Australia and New Zealand: a binational registry study.

BACKGROUND: Withdrawal from dialysis is an increasingly common cause of death in patients with end-stage kidney disease (ESKD). As most published reports of dialysis withdrawal have been outside the Oceania region, the aims of this study were to determine the frequency, temporal pattern and predictors of dialysis withdrawal in Australian and New Zealand patients receiving chronic haemodialysis. METHODS: This study included all people with ESKD in Australia and New Zealand who commenced chronic haemodialysis between 1 January 1997 and 31 December 2016, using data from the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Competing risk regression models were used to identify predictors of dialysis withdrawal mortality, using non-withdrawal cause of death as the competing risk event. RESULTS: Among 40 447 people receiving chronic haemodialysis (median age 62 years, 61% male, 9% Indigenous), dialysis withdrawal mortality rates increased from 1.02 per 100 patient-years (11% of all deaths) during the period 1997-2000 to 2.20 per 100 patient-years (32% of all deaths) during 2013-16 (P < 0.001). Variables that were significantly associated with a higher likelihood of haemodialysis withdrawal were older age {≥70 years subdistribution hazard ratio [SHR] 1.77 [95% confidence interval (CI) 1.66-1.89]; reference 60-70 years}, female sex [SHR 1.14 (95% CI 1.09-1.21)], white race [Asian SHR 0.56 (95% CI 0.49-0.65), Aboriginal and Torres Strait Islander SHR 0.83 (95% CI 0.74-0.93), Pacific Islander SHR 0.47 (95% CI 0.39-0.68), reference white race], coronary artery disease [SHR 1.18 (95% CI 1.11-1.25)], cerebrovascular disease [SHR 1.15 (95% CI 1.08-1.23)], chronic lung disease [SHR 1.13 (95% CI 1.06-1.21)] and more recent era [2013-16 SHR 3.96 (95% CI 3.56-4.48); reference 1997-2000]. CONCLUSIONS: Death due to haemodialysis withdrawal has become increasingly common in Australia and New Zealand over time. Predictors of haemodialysis withdrawal include older age, female sex, white race and haemodialysis commencement in a more recent era.

Temporal changes in dialysate [Na+] prescription from 1996 to 2018 and their clinical significance as judged from a meta-regression of clinical trials.

Over the last two decades, the clinical care of dialysis patients has refocused sharply on fluid volume control. Dialysate [Na+] is a key, albeit under-investigated, clinical tool for manipulation of fluid volume on dialysis. In the article, we firstly use data from the Dialysis Outcomes and Practice Patterns Study to document the global decrease in dialysate [Na+] that has occurred from 1996 to 2018, and demonstrate the virtual disappearance of [Na+] profiling from routine dialysis practice over the same period. Second, we used data from previously synthesized randomized clinical trial evidence combined with that of a more recently published trail to assess the clinical significance of these changes, estimating the effects of different levels of low dialysate [Na+] on key clinical outcomes. Our analyses suggest that current levels of dialysate [Na+] in some health jurisdictions are possibly causing harm to many patients, especially given that real world populations are significantly less robust and more vulnerable than clinical trial ones. To quote a recent editorial, "more evidence needed before lower dialysate sodium concentrations can be recommended." That evidence is coming, and no further changes should be made to default customary practice until it is available.

Can economic incentives increase the use of home dialysis?

There are advantages to home dialysis for patients, and kidney care programs, but use remains low in most countries. Health-care policy-makers have many levers to increase use of home dialysis, one of them being economic incentives. These include how health-care funding is provided to kidney care programs and dialysis facilities; how physicians are remunerated for care of home dialysis patients; and financial incentives-or removal of disincentives-for home dialysis patients. This report is based on a comprehensive literature review summarizing the impact of economic incentives for home dialysis and a workshop that brought together an international group of policy-makers, health economists and home dialysis experts to discuss how economic incentives (or removal of economic disincentives) might be used to increase the use of home dialysis. The results of the literature review and the consensus of workshop participants were that financial incentives to dialysis facilities for home dialysis (for instance, through activity-based funding), particularly in for-profit systems, could lead to a small increase in use of home dialysis. The evidence was less clear on the impact of economic incentives for nephrologists, and participants felt this was less important than a nephrologist workforce in support of home dialysis. Workshop participants felt that patient-borne costs experienced by home dialysis patients were unjust and inequitable, though participants noted that there was no evidence that decreasing patient-borne costs would increase use of home dialysis, even among low-income patients. The use of financial incentives for home dialysis-whether directed at dialysis facilities, nephrologists or patients-is only one part of a high-performing system that seeks to increase use of home dialysis.

Low dialysate sodium levels for chronic haemodialysis.

BACKGROUND: Cardiovascular (CV) disease is the leading cause of death in dialysis patients, and strongly associated with fluid overload and hypertension. It is plausible that low dialysate [Na+] may decrease total body sodium content, thereby reducing fluid overload and hypertension, and ultimately reducing CV morbidity and mortality. OBJECTIVES: This review evaluated harms and benefits of using a low (< 138 mM) dialysate [Na+] for maintenance haemodialysis (HD) patients. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 7 August 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs), both parallel and cross-over, of low (< 138 mM) versus neutral (138 to 140 mM) or high (> 140 mM) dialysate [Na+] for maintenance HD patients were included. DATA COLLECTION AND ANALYSIS: Two investigators independently screened studies for inclusion and extracted data. Statistical analyses were performed using random effects models, and results expressed as risk ratios (RR) for dichotomous outcomes, and mean differences (MD) or standardised MD (SMD) for continuous outcomes, with 95% confidence intervals (CI). Confidence in the evidence was assessed using GRADE. MAIN RESULTS: We included 12 studies randomising 310 patients, with data available for 266 patients after dropout. All but one study evaluated a fixed concentration of low dialysate [Na+], and one profiled dialysate [Na+]. Three studies were parallel group, and the remaining nine cross-over. Of the latter, only two used a washout between intervention and control periods. Most studies were short-term with a median (interquartile range) follow-up of 3 (3, 8.5) weeks. Two were of a single HD session, and two of a single week's HD. Half of the studies were conducted prior to 2000, and five reported use of obsolete HD practices. Risks of bias in the included studies were often high or unclear, lowering confidence in the results.Compared to neutral or high dialysate [Na+], low dialysate [Na+] had the following effects on "efficacy" endpoints: reduced interdialytic weight gain (10 studies: MD -0.35 kg, 95% CI -0.18 to -0.51; high certainty evidence); probably reduced predialysis mean arterial blood pressure (BP) (4 studies: MD -3.58 mmHg, 95% CI -5.46 to -1.69; moderate certainty evidence); probably reduced postdialysis mean arterial BP (MAP) (4 studies: MD -3.26 mmHg, 95% CI -1.70 to -4.82; moderate certainty evidence); probably reduced predialysis serum [Na+] (7 studies: MD -1.69 mM, 95% CI -2.36 to -1.02; moderate certainty evidence); may have reduced antihypertensive medication (2 studies: SMD -0.67 SD, 95% CI -1.07 to -0.28; low certainty evidence). Compared to neutral or high dialysate [Na+], low dialysate [Na+] had the following effects on "safety" endpoints: probably increased intradialytic hypotension events (9 studies: RR 1.56, 95% 1.17 to 2.07; moderate certainty evidence); probably increased intradialytic cramps (6 studies: RR 1.77, 95% 1.15 to 2.73; moderate certainty evidence).Compared to neutral or high dialysate [Na+], low dialysate [Na+] may make little or no difference to: intradialytic BP (2 studies: MD for systolic BP -3.99 mmHg, 95% CI -17.96 to 9.99; diastolic BP 1.33 mmHg, 95% CI -6.29 to 8.95; low certainty evidence); interdialytic BP (2 studies:, MD for systolic BP 0.17 mmHg, 95% CI -5.42 to 5.08; diastolic BP -2.00 mmHg, 95% CI -4.84 to 0.84; low certainty evidence); dietary salt intake (2 studies: MD -0.21g/d, 95% CI -0.48 to 0.06; low certainty evidence).Due to very low quality of evidence, it is uncertain whether low dialysate [Na+] changed extracellular fluid status, venous tone, arterial vascular resistance, left ventricular mass or volumes, thirst or fatigue. Studies did not examine cardiovascular or all-cause mortality, cardiovascular events, or hospitalisation. AUTHORS' CONCLUSIONS: It is likely that low dialysate [Na+] reduces intradialytic weight gain and BP, which are effects directionally associated with improved outcomes. However, the intervention probably also increases intradialytic hypotension and reduces serum [Na+], effects that are associated with increased mortality risk. The effect of the intervention on overall patient health and well-being is unknown. Further evidence is needed in the form of longer-term studies in contemporary settings, evaluating end-organ effects in small-scale mechanistic studies using optimal methods, and clinical outcomes in large-scale multicentre RCTs.

Hemofilter with Adsorptive Capacities: Case Report Series.

BACKGROUND: oXiris is a blood purification product that has been launched recently in China. In addition to renal function support and fluid management capabilities, it can also adsorb cytokines and endotoxins. This may complement standard treatment for septic acute kidney injury (AKI) patients to control the amplitude of systemic inflammatory response responsible for acute tissue and organ damage. Objectives of our study are to elucidate characteristics of septic AKI patients who respond to treatment with oXiris and to describe the performance of oXiris through patient cases in the absence of large randomized trials on clinical use of oXiris for septic AKI patients in China. SUMMARY: Here, we present 4 cases managed in intensive care units of major hospitals in China. Key practical aspects from an expert meeting discussing these cases have been included as guidance for the use of oXiris in septic AKI patients. Key Messages: Based on the experience gathered from 4 cases, oXiris should be used early in the treatment of septic AKI patients as an adjuvant therapy with good infection source control. It should not be used to delay or replace infection source control. These cases also demonstrated that patients with high risk of bleeding can use oXiris without additional anticoagulation for up to 36 h without implications on serum protein levels and platelet count. Short of definitive biomarkers to gauge the ideal blood purification initiation and discontinuation time for septic AKI patients, clinical judgment is key to determining optimal use of oXiris in septic AKI patients.

Incremental and twice weekly haemodialysis in Australia and New Zealand.

BACKGROUND: Haemodialysis is usually started at a frequency of three times a week, with occasional patients starting twice weekly ('incremental dialysis'). Incremental haemodialysis (HD) may preserve residual kidney function and has been associated with reduced mortality. In the present study, we report prevalence and outcomes of incremental dialysis in Australia and New Zealand. METHODS: The cohort was all adults starting renal replacement therapy with HD in Australia and New Zealand 2004-2015. We used cox proportional hazards modelling with a primary exposure of dialysis frequency at first survey date (≥ or <3 times per week). The primary outcome was all-cause mortality (primary), cardiovascular and non-cardiovascular mortality (secondary). RESULTS: Eight-hundred fifty of 27 513 subjects were started on twice weekly HD (prevalence 3%). Compared to conventional patients, incremental dialysis patients were older (67 vs 62 years, P < 0.001), had a lower body mass index (26.1 vs 27.7 kg/m2 , P < 0.001), had a higher starting estimated glomerular filtration rate (7.59 vs 6.66 mL/min P < 0.001) and had less diabetes (39.2% vs 50.2%, P < 0.001). In a multivariate model, incremental start dialysis was not associated with all-cause mortality (hazard ratio (HR) = 1.03, 95% confidence interval (CI) = 0.92-1.16) or cardiovascular mortality (HR = 0.87, 95% CI = 0.71-1.07), but was associated with an increased risk of non-cardiovascular mortality (HR = 1.25, 95% CI = 1.11-1.42). CONCLUSION: Incremental dialysis was used infrequently, and there was evidence of patient level differences. All-cause mortality was similar, but there were differences in cause specific mortality. Incremental dialysis needs to be tested in prospective trials to define the safety and efficacy of this approach.

Treatment of lead and arsenic poisoning in anuric patients - a case report and narrative review of the literature.

BACKGROUND: Heavy metal poisoning can cause debilitating illness if left untreated, and its management in anuric patients poses challenges. Literature with which to guide clinical practice in this area is rather scattered. CASE PRESENTATION: We present a case of symptomatic lead and arsenic poisoning from use of Ayurvedic medicine in a 28-year-old man with end-stage kidney disease on chronic hemodialysis. We describe his treatment course with chelating agents and extracorporeal blood purification, and review the relevant literature to provide general guidance. CONCLUSION: Cumulative clinical experience assists in identifying preferred chelators and modalities of extracorporeal blood purification when managing such patients. However, a larger body of real-world or clinical trial evidence is necessary to inform evidence-based guidelines for the management of heavy metal poisoning in anuric patients.

Recruitment and participant baseline characteristics in the dialysis outcomes in those aged 65 years or older study.

BACKGROUND: Despite an increasing number of older people commencing dialysis the impact of dialysis on their quality of life and survival, remains unclear. The Dialysis Outcomes in those aged over 65 years or older study is an accelerated prospective cohort longitudinal design study, designed to obtain sufficient health related quality of life data, linked to clinical data, to inform clinicians' and patients' decision-making with respect to end stage kidney disease (ESKD), outcomes, and options for management in New Zealand (NZ). METHODS: The study has an accelerated prospective cohort longitudinal design, comprised of cross-sectional and longitudinal components. We report the baseline data on the 225 participants enrolled in the study. Dialysis duration was grouped in tertiles from less than one year (incident patients), 1-3 years and greater than 3 years. Health related quality of life data was obtained from self-reported questionnaires including KDQoL-36, EQ-5D-3 L, FACIT, WHODAS II, and the Personal Well-being Score. RESULTS: The median age of the cohort was 71 years and two thirds were male. Three quarters of the participants were on dialysis at the baseline, with 42% of those on home dialysis (haemodialysis or peritoneal dialysis). Maori and Pacific people were over represented (20% Maori and 24% Pacific) in the sample, when compared to the general NZ population of the same age group (where 5% are Maori and 2% are Pacific). At baseline, there were no differences observed in sociodemographic, quality of life or health characteristics between the dialysis groups either by modality or duration of dialysis. CONCLUSIONS: We report the baseline characteristics of participants enrolled prospectively into a longitudinal cohort observational study examining health related quality of life factors with clinical characteristics on dialysis outcomes in a group of New Zealanders aged 65 years or older who are either on dialysis or have been educated about dialysis (BMC Nephrol 14:175, 2013). Subsequent publications are planned, analysing the prospective longitudinal data to identify key factors that determine both outcome and quality of life for individuals of this age group. TRIAL REGISTRATION: ACTRN12611000024943 .

Outcomes and practice patterns with hemodiafiltration in Shanghai: a longitudinal cohort study.

BACKGROUND: Globally, there is increased clinical interest and uptake of hemodiafiltration (HDF) for increased removal of uremic toxins. To date, there has been no epidemiological analysis of HDF in China. We present HDF practice patterns and associated mortality risk in Shanghai. METHODS: This is an observational, prospectively collected, retrospective analysis of 9351 Chinese patients initiating hemodialysis in Shanghai from 2007 to 2014. The primary exposure was hemodialysis sub-modality at inception, classified into hemodiafiltration (HDF) and hemodialysis (HD), with adjustment for concommitant hemoperfusion. The primary outcome was patient mortality. We used Cox proportional hazards regression and Fine and Gray's proportional subhazards regression, with multiple imputation of missing co-variates by the chained equation method, adjusting for demographic and clinical variables. RESULTS: Overall, patients in the cohort were younger, with a more males, and with a lower body mass index when compared to corresponding non-Asian cohorts. Mortality rate was low although it doubled over the period of observation. HDF utilization increased from 7% of patients in 2007 to 42% of patients in 2014. The majority of patients received HDF once a week. The adjusted hazard ratio of death (95% confidence intervals) for HDF versus HD was 0.85 (0.71-1.03), and corresponding sub-hazard ratio 0.86 (0.71-1.03). There was strong effect modification by age. In those aged 40-60 years, the hazard ratio (95% confidence intervals) was 0.65 (0.45-0.94), and sub-hazard ratio also 0.65 (0.45-0.95). CONCLUSIONS: Our study has certain limitations resulting from the limited number of co-variates available for modelling, missing data for some co-variates, and the lack of verification of data against source documentation. Notwithstanding, there is evidence of clinical benefit from HDF in China, and potential to improve patient outcomes through the greater removal of middle and larger uremic solutes.

Intensive hemodialysis-keeping the faith.

In this issue of Kidney International, Tennankore et al. present a robust observational study that evaluates different submodalities of intensive hemodialysis. Their paper addresses a critical question, but more importantly illustrates the limits of statistical adjustment when there is major crossover between groups and important center effect. Intensive hemodialysis remains a strong contender to meet the needs of modern patients, and-no matter how challenging-well-deserving of further definitive study in clinical trials.

Biocompatibility of a new PD solution for Japan, Reguneal™, measured as in vitro proliferation of fibroblasts.

BACKGROUND: The aim of this study was to investigate in vitro biocompatibility of Reguneal™, a new bicarbonate containing peritoneal dialysis fluid (PDF) for Japan, and compare it with other PDFs available in that country. METHODS: We assessed basal cytotoxicity using in vitro proliferation of cultured fibroblasts, L-929, determining the quantity of living cells by the uptake of Neutral Red. Levels of ten glucose degradation products (GDPs) were measured by a validated ultrahigh-performance liquid chromatography method in combination with an ultraviolet detector. We compared inhibition of fibroblast cell growth between brands of PDF, adjusting for dextrose and GDP concentrations using random-effects mixed models. RESULTS: The results demonstrate that cytotoxicity of Reguneal™ is comparable to a sterile-filtered control and is less cytotoxic than most of the other PDFs, most of which significantly inhibited cell growth. As a "class effect", increasing dextrose and GDP concentrations were non-significantly but positively associated with cytotoxicity. As a "brand effect", these relationships varied widely between brands, and some PDFs had significant residual effects on basal cytotoxicity through mechanisms that were unassociated with either dextrose or GDP concentration. CONCLUSION: Our study suggests that Reguneal™ is a biocompatible PDF. The results of our study also highlight that dextrose and GDPs are important for biocompatibility, but alone are not a complete surrogate. The results of our study need to be confirmed in other tissue culture models, and should lead to further research on determinants of biocompatibility and the effect of such PDFs on clinical outcomes.

Comparing dialysis centre mortality outcomes across Australia and New Zealand: identifying unusually performing centres 2008-2013.

BACKGROUND: Comparing the mortality profiles of dialysis centres is important to ensure that high standards of care are maintained. We compare the performance of dialysis centres in Australia and New Zealand in their treatment of haemodialysis patients, accounting for the competing risks of kidney transplantation and transfer to peritoneal dialysis. METHODS: Observational cohort study. We included data from all adult patients (5574 patients) commencing haemodialysis at home or in a facility between 2008 and 2010 across 62 dialysis centres, from the Australia and New Zealand Dialysis and Transplant Registry. Standardised mortality ratios were calculated by estimating mortality probabilities from a pooled random effects logistic regression model, accounting for the competing risk of transplantation using an inverse probability weighting approach. Models were adjusted for patient comorbidities, sex, height, weight, late referral to a nephrologist, age, race, primary kidney disease, smoking status, and serum creatinine (µmol/l). RESULTS: Two dialysis centres were found to have relatively higher levels of risk-adjusted mortality lying outside the prediction intervals for "usual" performance. Risk adjusted mortality rates were not associated with centres' compliance with guidelines for vascular access and biochemical and haematological targets. CONCLUSIONS: We demonstrate that standardised mortality ratios are useful to identify facilities that have statistically outlying mortality risk. Our criterion for determining whether a centre has better or worse performance than expected is statistical, and thus analyses such as ours can serve only as a screening tool, and are only one aspect of assessment of "quality" of performance.

Measuring the patient response to dialysis therapy: hemodiafiltration and clinical trials.

There is a strong biological plausibility for benefit from removal of larger uremic toxins and increasing positive clinical experience with hemodiafiltration. However, evidence supporting hemodiafiltration is not definitive with studies that are often limited by serious methodological shortcomings. Morena et al. show that hemodiafiltration may prevent intradialytic hypotension, albeit in a study that also has some shortcomings. Ongoing research for hemodiafiltration is still needed through high-quality clinical trials that adhere to standards for clinical trial conduct and reporting.

Fatal Dialysis Vascular Access Hemorrhage.

Bleeding from dialysis vascular access (arteriovenous fistulas, arteriovenous grafts, and vascular catheters) is uncommon. Death from these bleeds is rare and likely to be under-reported, with incident rates of fewer than 1 episode for every 1,000 patient-years on dialysis, meaning that dialysis units may experience this catastrophic event only once a decade. There is an opportunity to learn from (and therefore prevent) these bleeding deaths. We reviewed all reported episodes of death due to vascular access bleeding in Australia and New Zealand over a 14-year period together with individual dialysis units' root cause analyses on each event. In this perspective, we provide a clinically useful summary of the evidence and knowledge gained from these rare events. Our conclusion is that death due to dialysis vascular access hemorrhage is an uncommon, catastrophic, but potentially preventable event if the right policies and procedures are put in place.