Effect of Hemodiafiltration or Hemodialysis on Mortality in Kidney Failure.

BACKGROUND: Several studies have suggested that patients with kidney failure may benefit from high-dose hemodiafiltration as compared with standard hemodialysis. However, given the limitations of the various published studies, additional data are needed. METHODS: We conducted a pragmatic, multinational, randomized, controlled trial involving patients with kidney failure who had received high-flux hemodialysis for at least 3 months. All the patients were deemed to be candidates for a convection volume of at least 23 liters per session (as required for high-dose hemodiafiltration) and were able to complete patient-reported outcome assessments. The patients were assigned to receive high-dose hemodiafiltration or continuation of conventional high-flux hemodialysis. The primary outcome was death from any cause. Key secondary outcomes were cause-specific death, a composite of fatal or nonfatal cardiovascular events, kidney transplantation, and recurrent all-cause or infection-related hospitalizations. RESULTS: A total of 1360 patients underwent randomization: 683 to receive high-dose hemodiafiltration and 677 to receive high-flux hemodialysis. The median follow-up was 30 months (interquartile range, 27 to 38). The mean convection volume during the trial in the hemodiafiltration group was 25.3 liters per session. Death from any cause occurred in 118 patients (17.3%) in the hemodiafiltration group and in 148 patients (21.9%) in the hemodialysis group (hazard ratio, 0.77; 95% confidence interval, 0.65 to 0.93). CONCLUSIONS: In patients with kidney failure resulting in kidney-replacement therapy, the use of high-dose hemodiafiltration resulted in a lower risk of death from any cause than conventional high-flux hemodialysis. (Funded by the European Commission Research and Innovation; CONVINCE Dutch Trial Register number, NTR7138.).

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.

Randomized trial comparing standard versus thermocontrolled haemodialysis using intradialytic cardiac, brain and renal magnetic resonance imaging.

BACKGROUND: Ischaemic end-organ damage during haemodialysis (HD) is a significant problem that may be ameliorated by intradialytic cooling. A randomised trial was performed to compare standard HD (SHD; dialysate temperature 37°C) and programmed cooling of the dialysate [thermocontrolled HD (TCHD)] using multiparametric magnetic resonance imaging (MRI) to assess structural, functional and blood flow changes in the heart, brain and kidneys. METHODS: Prevalent HD patients were randomly allocated to receive either SHD or TCHD for 2 weeks before undergoing serial MRI at four time points: pre-, during (30 min and 180 min) and post-dialysis. MRI measures include cardiac index, myocardial strain, longitudinal relaxation time (T1), myocardial perfusion, internal carotid and basilar artery flow, grey matter perfusion and total kidney volume. Participants then crossed to the other modality to repeat the study protocol. RESULTS: Eleven participants completed the study. Separation in blood temperature between TCHD (-0.1 ± 0.3°C) and SHD (+0.3 ± 0.2°C; P = .022) was observed, although there was no difference in tympanic temperature changes between arms. There were significant intradialytic reductions in cardiac index, cardiac contractility (left ventricular strain), left carotid and basilar artery blood flow velocities, total kidney volume, longitudinal relaxation time (T1) of the renal cortex and transverse relaxation rate (T2*) of the renal cortex and medulla, but no differences between arms. Pre-dialysis T1 of the myocardium and left ventricular wall mass index were lower after 2 weeks of TCHD compared with SHD [1266 ms (interquartile range 1250-1291) versus 1311 ± 58 ms, P = .02; 66 ± 22 g/m2 versus 72 ± 23 g/m2, P = .004]. CONCLUSIONS: HD adversely affects cardiac function, reduces carotid and basilar artery blood flow and total kidney volume, but mild dialysate cooling using a biofeedback module did not result in differences in intradialytic MRI measures compared with SHD.

Hyponatraemia and fluid overload are associated with higher risk of mortality in dialysis patients.

BACKGROUND: The 5-year mortality rate for haemodialysis patients is over 50%. Acute and chronic disturbances in salt and fluid homeostasis contribute to poor survival and are established as individual mortality risk factors. However, their interaction in relation to mortality is unclear. METHODS: We used the European Clinical Database 5 to investigate in a retrospective cohort analysis the relationship between transient hypo- and hypernatremia, fluid status and mortality risk of 72 163 haemodialysis patients from 25 countries. Incident haemodialysis patients with at least one valid measurement of bioimpedance spectroscopy were followed until death or administrative censoring from 1 January 2010 to 4 December 2019. Fluid overload and depletion were defined as >2.5 L above, and -1.1 L below normal fluid status, respectively. N = 2 272 041 recorded plasma sodium and fluid status measurements were available over a monthly time grid and analysed in a Cox regression model for time-to-death. RESULTS: Mortality risk of hyponatremia (plasma sodium <135 mmol/L) was slightly increased when fluid status was normal [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.18-1.35], increased by half when patients were fluid depleted (HR 1.56, 95% CI 1.27-1.93) and accelerated during fluid overload (HR 1.97, 95% CI 1.82-2.12). CONCLUSIONS: Plasma sodium and fluid status act independently as risk factors on mortality. Patient surveillance of fluid status is especially important in the high-risk subpopulation of patients with hyponatremia. Prospective patient-level studies should examine the effects of chronic hypo- and hypernatremia, risk determinants, and their outcome risk.

Long-term peridialytic blood pressure changes are related to mortality.

BACKGROUND: In chronic haemodialysis (HD) patients, the relationship between long-term peridialytic blood pressure (BP) changes and mortality has not been investigated. METHODS: To evaluate whether long-term changes in peridialytic BP are related to mortality and whether treatment with HD or haemodiafiltration (HDF) differs in this respect, the combined individual participant data of three randomized controlled trials comparing HD with HDF were used. Time-varying Cox regression and joint models were applied. RESULTS: During a median follow-up of 2.94 years, 609 of 2011 patients died. As for pre-dialytic systolic BP (pre-SBP), a severe decline (≥21 mmHg) in the preceding 6 months was independently related to increased mortality [hazard ratio (HR) 1.61, P = .01] when compared with a moderate increase. Likewise, a severe decline in post-dialytic diastolic BP (DBP) was associated with increased mortality (adjusted HR 1.96, P < .0005). In contrast, joint models showed that every 5-mmHg increase in pre-SBP and post-DBP during total follow-up was related to reduced mortality (adjusted HR 0.97, P = .01 and 0.94, P = .03, respectively). No interaction was observed between BP changes and treatment modality. CONCLUSION: Severe declines in pre-SBP and post-DBP in the preceding 6 months were independently related to mortality. Therefore peridialytic BP values should be interpreted in the context of their changes and not solely as an absolute value.

Water and dialysis fluid purity for contemporary hemodialysis.

INTRODUCTION: The purity of water and dialysis fluids is of utmost importance in ensuring the safe and effective administration of hemodialysis treatment to patients with chronic kidney disease. It is crucial to enforce compliance with international standards for dialysis water and fluids, as this is mandatory in reducing chemical hazards, mitigating the adverse effects of bioincompatibility resulting from contaminated water and ultimately enhancing long-term patient outcomes. STANDARDS AND RISKS: Within this comprehensive review, we highlight the presence of water contaminants and thoroughly assess the existing international standards for dialysis water and fluids, spanning from pure to ultrapure. Additionally, we delve into the fundamental components of water purification and present a comprehensive range of water treatment options, encompassing pre-treatment, primary treatment (reverse osmosis), and tertiary water treatment. Furthermore, we outline recommended monitoring and maintenance procedures, ensuring the consistent delivery of high-quality water and dialysis fluids at the point of care. WATER PURIFICATION AND MONITORING SUSTAINABILITY AND FUTURE CHALLENGES: Importantly, we raise concerns regarding the sustainability and conservation of water resources in hemodialysis treatment. It is imperative that these concerns be addressed in the future to avert the potential shortage of this essential resource. CONCLUSION: In conclusion, the contemporary landscape of hemodialysis conditions has engendered an urgent necessity for advanced water treatment systems and optimized delivery of dialysis fluids. This review serves as a comprehensive update on the latest technological advancements aimed at meeting these critical demands. Dialysis water and fluids must adhere to increasingly stringent purity constraints, encompassing both biochemical and microbiological perspectives.

Systematic review to compare the outcomes associated with the modalities of expanded hemodialysis (HDx) versus high-flux hemodialysis and/or hemodiafiltration (HDF) in patients with end-stage kidney disease (ESKD).

BACKGROUND: This systematic review was performed to identify recent published comparative evidence on the efficacy, effectiveness, and safety of expanded hemodialysis (HDx) versus high-flux HD and/or hemodiafiltration (HDF) for long-term outcomes in end-stage kidney disease. METHODS: Systematic literature review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. Medline, Medline® Epub Ahead of Print, EconLit, Embase, and EBM reviews were searched to identify relevant publications from 2013 onwards. Eligibility criteria included clinical studies reporting mortality, hospitalizations, cardiovascular outcomes, economic evaluations, cost studies, and quality of life (QoL) studies. RESULTS: A total of 79 relevant studies were identified with 29 prioritized for detailed analysis; four compared HDx to HD, one compared HDF and HDx, and 24 compared HDF with HD. A total of 13 randomized controlled trial (RCT)-based studies were identified; 11 compared HDF with HD, one compared HDx with HD, and one compared HDF with HDx. Follow-up duration ranged from 16 weeks to 7 years for HDF studies and from 12 weeks to 1 year for HDx studies. HDF showed significant improvements in mortality, cardiovascular outcomes, hospitalizations, and QoL versus high-flux HD. One study reported mortality outcomes for HDx and found no difference versus HDF. QoL benefits with HDx were reported in a small number of studies. CONCLUSION: The efficacy and safety of HDF is supported by a robust evidence base that includes several RCTs. While HDx may offer benefits over high-flux HD, long-term studies are required to compare HDx with online high volume HDF. REGISTRATION: PROSPERO registration number: CRD42022301009.

Sodium flux during hemodialysis and hemodiafiltration treatment of acute kidney injury: Effects of dialysate and infusate sodium concentration at 140 and 145 mmol/L.

BACKGROUND: A higher sodium (Na) dialysate concentration is recommended during renal replacement therapy (RRT) of acute kidney injury (AKI) to improve intradialytic hemodynamic tolerance, but it may lead to Na loading to the patient. We aimed to evaluate Na flux according to Na dialysate and infusate concentrations at 140 and 145 mmol/L during hemodialysis (HD) and hemodiafiltration (HDF). METHODS: Fourteen AKI patients that underwent consecutive HD or HDF sessions with Na dialysate/infusate at 140 and 145 mmol/L were included. Per-dialytic flux of Na was estimated using mean sodium logarithmic concentration including diffusive and convective influx. We compared the flux of sodium between HD140 and 145, and between HDF140 and 145. RESULTS: Nine HD140, ten HDF140, nine HD145, and 11 HDF145 sessions were analyzed. A Na gradient from the dialysate/replacement fluid to the patient was observed with dialysate/infusate Na at 145 mmol/L in both HD and HDF (p = 0.01). The comparison of HD145 to HD140 showed that higher Na dialysate induced a diffusive Na gradient to the patient (163 mmol vs. -25 mmol, p = 0.004) and that of HDF145 to -140 (211 vs. 36 mmol, p = 0.03) as well. Intradialytic hemodynamic tolerance was similar across all RRT sessions. CONCLUSIONS: During both HD and HDF, a substantial Na loading occurred with a Na dialysate and infusate at 145 mmol/L. This Na loading is smaller in HDF with Na dialysate and infusate concentration at 140 mmol/L and inversed with HD140. Clinical and intradialytic hemodynamic tolerance was fair regardless of Na dialysate and infusate.

Personalized Management of Sodium and Volume Imbalance in Hemodialysis to Mitigate High Costs of Hospitalization.

The primary objective of hemodialysis (HD) is lowering concentrations of organic uremic toxins that accumulate in blood in end-stage kidney disease (ESKD) and redress imbalances of inorganic compounds in particular sodium and water. Removal by ultrafiltration of excess fluid that has accumulated during the dialysis-free interval is a vital aspect of each HD session. Most HD patients are volume overloaded, with ∼25% of patients having severe (>2.5 L) fluid overload (FO). The potentially serious complications of FO contribute to the high cardiovascular morbidity and mortality observed in the HD population. Weekly cycles imposed by the schedule of HD treatments create a deleterious and unphysiological "tide phenomenon" marked by sodium-volume overload (loading) and depletion (unloading). Fluid overload-related hospitalizations are frequent and costly, with average cost estimates of $ 6,372 per episode, amounting to some $ 266 million total costs over a 2-year period in a US dialysis population. Various strategies (e.g., dry weight management or use of fluids with different sodium concentrations) have been attempted to rectify FO in HD patients but have met with limited success largely due to imprecise and cumbersome, or costly, approaches. In recent years, conductivity-based technologies have been refined to actively restore sodium and fluid imbalance and maintain the predialysis plasma sodium set point (plasma tonicity) of each patient. By automatically controlling the dialysate-plasma sodium gradient based on the specific patient needs throughout a session, an individualized sodium dialysate prescription can be delivered. Maintaining precise sodium mass balance helps better control of blood pressure, reduces FO, and thus tends to prevent hospitalization for congestive heart failure. We present the case for personalized salt and fluid management via a machine-integrated sodium management tool. Results from proof-of-principle clinical trials indicate that the tool enables individualized sodium-fluid volume control during each HD session. Its application in routine clinical practice has the potential to mitigate the substantial economic burden of hospitalizations attributed to volume overload complications in HD. Additionally, such a tool would contribute toward reduced symptomology and dialysis-induced multiorgan damage in HD patients and to improving their treatment perception and quality of life which matters most to patients.

Assessment of a serum calcification propensity test for the prediction of all-cause mortality among hemodialysis patients.

BACKGROUND: Vascular calcification is a major contributor to the high cardiac burden among hemodialysis patients. A novel in vitro T50-test, which determines calcification propensity of human serum, may identify patients at high risk for cardiovascular (CV) disease and mortality. We evaluated whether T50 predicts mortality and hospitalizations among an unselected cohort of hemodialysis patients. METHODS: This prospective clinical study included 776 incident and prevalent hemodialysis patients from 8 dialysis centers in Spain. T50 and fetuin-A were determined at Calciscon AG, all other clinical data were retrieved from the European Clinical Database. After their baseline T50 measurement, patients were followed for two years for the occurrence of all-cause mortality, CV-related mortality, all-cause and CV-related hospitalizations. Outcome assessment was performed with proportional subdistribution hazards regression modelling. RESULTS: Patients who died during follow-up had a significantly lower T50 at baseline as compared to those who survived (269.6 vs. 287.7 min, p = 0.001). A cross-validated model (mean c statistic: 0.5767) identified T50 as a linear predictor of all-cause-mortality (subdistribution hazard ratio (per min): 0.9957, 95% CI [0.9933;0.9981]). T50 remained significant after inclusion of known predictors. There was no evidence for prediction of CV-related outcomes, but for all-cause hospitalizations (mean c statistic: 0.5284). CONCLUSION: T50 was identified as an independent predictor of all-cause mortality among an unselected cohort of hemodialysis patients. However, the additional predictive value of T50 added to known mortality predictors was limited. Future studies are needed to assess the predictive value of T50 for CV-related events in unselected hemodialysis patients.

CONVINCE in the context of existing evidence on haemodiafiltration.

Haemodiafiltration (HDF) provides a greater removal of larger solutes and protein-bound compounds than conventional high-flux haemodialysis (HD). There are indications that the patients receiving the highest convection volumes of HDF result in improved survival compared with HD. However, the comparative efficacy of HDF versus HD remains unproven. Here we provide a comparative account of the methodology and aims of 'the comparison of high-dose HDF with high-flux HD' (CONVINCE) study in the context of the totality of evidence and how this study will contribute to reaching a higher level of certainty regarding the comparative efficacy of HDF versus HD in people with end-stage kidney disease.

The rationale and clinical potential of on-line hemodiafiltration as renal replacement therapy.

On-line hemodiafiltration (ol-HDF) was developed in the 1980s in response to the unmet medical needs observed with conventional low- and high-flux hemodialysis. Firstly, the limited overall efficacy of conventional HD treatment programs as compared to native kidney function has been consistently documented over the broad MW spectrum of uremic toxins as well as fluid volume and hemodynamic control. Secondly, the unphysiological profile of intermittent treatment leading to repetitive dialysis-induced hemodynamic stress is now a well-recognized component of cardiovascular disease and end organ damage. Thirdly, the bioincompatibility of patient-dialysis system leading to dialysis-induced biological reactions also identified as contributing to dialytic morbidity and mortality. To overcome these limitations and pitfalls, alternative convective-based therapies (hemofiltration and hemodiafiltration), using higher hemoincompatible membranes and ultrapure dialysis fluid, were proposed as a solution to enhance and enlarge MW spectrum of uremic compounds cleared and to reduce dialysis-patient biological interactions. In this context, online HDF appeared soon as the best viable and efficient renal replacement modality to cover these needs. Clinical development and implementation of ol-HDF showed also that dialytic convective dose matters with a threshold point (23 L/1.73 m2 in postdilution mode) to observe clinical benefits and outcomes improvements.

Prescription of online hemodiafiltration (ol-HDF).

HDF prescription should be able to satisfy the delivery of an optimal dialytic convective dose. Several factors are implicated in this endeavor. High blood flow rate is crucial to warranty processing an adequate blood volume and to ensure the highest shear rate per fiber needed to cleanse and prevent membrane fouling. A highly permeable dialyzer is needed with a surface area aligned to blood flow and performance needs. Anticoagulation requires specific adaptation in case of low molecular weight heparin use. By default, HDF prescription modality should ideally start by postdilution mode with a stepwise increment of convective dose by probing patient tolerance and efficacy. Alternative substitution modality should be considered if dialytic convective dose could not be achieved in the usual time frame. Convective dose prescription relies either on a manual mode (pressure control or volume control) or on automated mode (ultrafiltration control) depending on the technical options of the HDF machines. Dialysate flow rate is regulated by the HDF machine but should preferably keep constant dialysis fluid flowing the dialyzer with a Qb:Qd ratio of 1.4. Treatment time should not be reduced with HDF prescription. Treatment time should fit with patient tolerance (hemodynamic, osmotic, and solute shifts) and overall solute removal efficiency. Electrolytic prescription does not require specific adjustments as compared with conventional dialysis, but the patient needs to be monitored regularly and dialysate electrolyte adjusted to lab tests. A stepwise approach for implementing ol-HDF is preferable depending on the initial condition of the patient. Three particular cases may be considered: late-stage chronic kidney disease patient transitioning to renal replacement therapy, stable dialysis patient switching to HDF, and unstable or fragile patient or specific treatment schedule. Optimal dosing of HDF and personalized care to ensure treatment adequacy is the main goal for renal replacement therapy to improve patient outcomes. That should be ensured with HDF treatment.

On-line hemodiafiltration therapy for end-stage kidney disease patients: Promises for the future? What's next?

On-line hemodiafiltration (OL-HDF) is currently the most advanced form of blood purification modality leading convective-based therapies in end-stage kidney disease patients. By adding a high convective component to the diffusive clearance achieved with highly permeable dialyzers, OL-HDF reinforces removal of small MWt compounds and enlarges the spectrum of uremic compounds cleared up to middle and large MWt compounds. The biological and clinical benefits of convective-based therapy are currently also being explored in a revisited hybrid modality, combining an increased internal filtration process with a more open membrane. Regular use of ultrapure dialysis fluid required by convective-based therapies improves the bio-incompatibility of the extracorporeal circuit so reducing inflammatory responses. On-line production of substitution fluid, relying on a cold sterilization by ultrafiltration, has several advantages: First, it is a safe and established process; and second, it provides an unlimited amount of substitution fluid at the same cost as regular ultrapure dialysis fluid. As such, OL-HDF is adaptable to all substitution modalities (post, pre, or mixed-HDF), thus allowing the dialytic convective dose to be adjusted to the individual patient needs. The development of OL-HDF opens new pathways such as task automation simplifying care workflow. All these features make OL-HDF the most versatile dialysis modality that can be now integrated in various treatment schedules according to session time and frequency (daily, nocturnal, or alternate day) or location (incenter, satellite, or potentially home-based therapy).

Why and how high volume hemodiafiltration may reduce cardiovascular mortality in stage 5 chronic kidney disease dialysis patients? A comprehensive literature review on mechanisms involved.

Online hemodiafiltration (HDF) is an established renal replacement modality for patients with end stage chronic kidney disease that is now gaining rapid clinical acceptance worldwide. Currently, there is a growing body of evidence indicating that treatment with HDF is associated with better outcomes and reduced cardiovascular mortality for dialysis patients. In this comprehensive review, we provide an update on the potential mechanisms which may improve survival in HDF treated patients. The strongest evidence is for better hemodynamic stability and reduced endothelial dysfunction associated with HDF treatments. Clinically, this is marked by a reduced incidence of intradialytic hypotensive episodes, with a better hemodynamic response to ultrafiltration, mediated by an increase in total peripheral vascular resistance and extra-vascular fluid recruitment, most likely driven by the negative thermal balance associated with online HDF therapy. In addition, endothelial function appears to be improved due to a combination of a reduction of the inflammatory and oxidative stress complex syndrome and exposure to circulating cardiovascular uremic toxins. Reports of reversed cardiovascular remodeling effects with HDF may be confounded by volume and blood pressure management, which are strongly linked to center clinical practices. Currently, treatment with HDF appears to improve the survival of dialysis patients predominantly due to a reduction in their cardiovascular burden, and this reduction is linked to the sessional convection volume exchanged.

The oxygen cascade in patients treated with hemodialysis and native high-altitude dwellers: lessons from extreme physiology to benefit patients with end-stage renal disease.

Patients treated with hemodialysis (HD) repeatedly undergo intradialytic low arterial oxygen saturation and low central venous oxygen saturation, reflecting an imbalance between upper body systemic oxygen supply and demand, which are associated with increased mortality. Abnormalities along the entire oxygen cascade, with impaired diffusive and convective oxygen transport, contribute to the reduced tissue oxygen supply. HD treatment impairs pulmonary gas exchange and reduces ventilatory drive, whereas ultrafiltration can reduce tissue perfusion due to a decline in cardiac output. In addition to these factors, capillary rarefaction and reduced mitochondrial efficacy can further affect the balance between cellular oxygen supply and demand. Whereas it has been convincingly demonstrated that a reduced perfusion of heart and brain during HD contributes to organ damage, the significance of systemic hypoxia remains uncertain, although it may contribute to oxidative stress, systemic inflammation, and accelerated senescence. These abnormalities along the oxygen cascade of patients treated with HD appear to be diametrically opposite to the situation in Tibetan highlanders and Sherpa, whose physiology adapted to the inescapable hypobaric hypoxia of their living environment over many generations. Their adaptation includes pulmonary, vascular, and metabolic alterations with enhanced capillary density, nitric oxide production, and mitochondrial efficacy without oxidative stress. Improving the tissue oxygen supply in patients treated with HD depends primarily on preventing hemodynamic instability by increasing dialysis time/frequency or prescribing cool dialysis. Whether dietary or pharmacological interventions, such as the administration of L-arginine, fermented food, nitrate, nuclear factor erythroid 2-related factor 2 agonists, or prolyl hydroxylase 2 inhibitors, improve clinical outcome in patients treated with HD warrants future research.

Recent advances in dialysis membranes.

PURPOSE OF REVIEW: Improvement in hemodialysis treatment and membrane technology are focused on two aims: the first one is to achieve a better control of circulating uremic solutes by enhancing removal capacity and by broadening molecular weight spectrum of solutes cleared; the second one is to prevent inflammation by improving hemocompatibility of the global dialysis system. RECENT FINDINGS: Despite impressive progresses in polymers chemistry few hazards are still remaining associated with leaching or sensitization to polymer additives. Research has focused on developing more stable polymers by means of additives or processes aiming to minimize such risks. Membrane engineering manufacturing with support of nanocontrolled spinning technology has opened up membrane to middle and large molecular weight substances, while preserving albumin losses. Combination of diffusive and enhanced convective fluxes in the same hemodialyzer module, namely hemodiafiltration, provides today the highest solute removal capacity over a broad spectrum of solutes. SUMMARY: Dialysis membrane is a crucial component of the hemodialysis system to optimize solute removal efficacy and to minimize blood membrane biological reactions. Hemodialyzer is much more than a membrane. Dialysis membrane and hemodialyzer choice are parts of a treatment chain that should be operated in optimized conditions and adjusted to patient needs and tolerance, to improve patient outcomes.

Evolution of body composition and wasting indicators by time of day of haemodialysis.

BACKGROUND: It has been a long-standing clinical concern that haemodialysis (HD) patients on afternoon shifts (ASs) are more prone to protein-energy wasting (PEW) than those on morning shifts (MSs), as their dialysis scheme and post-dialysis symptoms may interfere with meal intake. We evaluated the effect of time of day of HD on the evolution of body composition changes and PEW surrogates. METHODS: We conducted a retrospective study among 9.963 incident HD patients treated in NephroCare centres (2011-16); data were routinely collected in the European Clinical Database. The course of multi-frequency bioimpedance determined lean and fat tissue indices (LTI and FTI) between patients in MSs/ASs over 2 years were compared with linear mixed models. Secondary PEW indicators were body mass index, albumin, creatinine index and normalized protein catabolic rate. Models included fixed (age, sex, vascular access and diabetes mellitus) and random effects (country and patient). RESULTS: Mean baseline LTI and FTI were comparable between MSs (LTI: 12.5 ± 2.9 kg/m2 and FTI: 13.7 ± 6.0 kg/m2) and ASs (LTI: 12.4 ± 2.9 kg/m2 and FTI: 13.2 ± 6.1 kg/m2). During follow-up, LTI decreased and FTI increased similarly, with a mean absolute change (baseline to 24 months) of -0.3 kg/m2 for LTI and +1.0 kg/m2 for FTI. The course of these malnutrition indicators did not differ between dialysis shifts (P for interaction ≥0.10). We also did not observe differences between groups for secondary PEW indicators. CONCLUSIONS: This study suggests that a dialysis shift in the morning or in the afternoon does not impact the long-term nutritional status of HD patients. Regardless of time of day of HD, patients progressively lose muscle mass and increase body fat.

Quantitative assessment of sodium mass removal using ionic dialysance and sodium gradient as a proxy tool: Comparison of high-flux hemodialysis versus online hemodiafiltration.

Restoration and maintenance of sodium are still a matter of concern and remains of critical importance to improve the outcomes in homeostasis of stage 5 chronic kidney disease patients on dialysis. Sodium mass balance and fluid volume control rely on the "dry weight" probing approach consisting mainly of adjusting the ultrafiltration volume and diet restrictions to patient needs. An additional component of sodium and fluid management relies on adjusting the dialysate-plasma sodium concentration gradient. Hypotonicity of ultrafiltrate in online hemodiafiltration (ol-HDF) might represent an additional risk factor in regard to sodium mass balance. A continuous blood-side approach for quantifying sodium mass balance in hemodialysis and ol-HDF using an online ionic dialysance sensor device ("Flux" method) embedded on hemodialysis machine was explored and compared to conventional cross-sectional "Inventory" methods using anthropometric measurement (Watson), multifrequency bioimpedance analysis (MF-BIA), or online clearance monitoring (OCM) to assess the total body water. An additional dialysate-side approach, consisting of the estimation of inlet/outlet sodium mass balance in the dialysate circuit was also performed. Ten stable hemodialysis patients were included in an "ABAB"-designed study comparing high-flux hemodialysis (hf-HD) and ol-HDF. Results are expressed using a patient-centered sign convention as follows: accumulation into the patient leads to a positive balance while recovery in the external environment (dialysate, machine) leads to a negative balance. In the blood-side approach, a slight difference in sodium mass transfer was observed between models with hf-HD (-222.6 [-585.1-61.3], -256.4 [-607.8-43.7], -258.9 [-609.8-41.3], and -258.5 [-607.8-43.5] mmol/session with Flux and Inventory models using VWatson , VMF-BIA , and VOCM values for the volumes of total body water, respectively; global P value < .0001) and ol-HDF modalities (-235.3 [-707.4-128.3], -264.9 [-595.5-50.8], -267.4 [-598.1-44.1], and -266.0 [-595.6-55.6] mmol/session with Flux and Inventory models using VWatson , VMF-BIA , and VOCM values for the volumes of total body water, respectively; global P value < .0001). Cumulative net ionic mass balance on a weekly basis remained virtually similar in hf-HD and ol-HDF using Flux method (P = n.s.). Finally, the comparative quantification of sodium mass balance using blood-side (Ionic Flux) and dialysate-side approaches reported clinically acceptable (a) agreement (with limits of agreement with 95% confidence intervals (CI): -166.2 to 207.2) and (b) correlation (Spearman's rho = 0.806; P < .0001). We validated a new method to quantify sodium mass balance based on ionic mass balance in dialysis patients using embedded ionic dialysance sensor combined with dialysate/plasma sodium concentrations. This method is accurate enough to support caregivers in managing sodium mass balance in dialysis patients. It offers a bridging solution to automated sodium proprietary balancing module of hemodialysis machine in the future.

Practice Patterns and Outcomes of Online Hemodiafiltration: A Real-World Evidence Study in a Russian Dialysis Network.

BACKGROUND: Evidence suggests that online hemodiafiltration (OL-HDF) is associated with improved survival. Whether the dose-response relationship between convective volume and mortality may be confounded by selection bias or descends from practice patterns is not clear. We sought to evaluate the role of patients' characteristics and practice patterns on OL-HDF dose and mortality in a large private dialysis network in the Republic of Russia. METHODS: In this multicenter, historical cohort study, we included adult incident patients on OL-HDF with at least 90 days of survival on renal replacement therapy in centers belonging to the Russian Federation Fresenius Medical Care network (January 1, 2011, to December 31, 2016). We evaluated predictors and outcomes (survival) of substitution volume target achievement (Qsub > 21 L/session). RESULTS: Among 1,081 enrolled patients, the average Qsub was 22.9 (±3.2) L/session; the mean ultrafiltration volume was 1.6 (±0.8) L/session. The mean age was 55.8 ± 13.2; 42% were woman. Most common comorbidities were congestive heart failure (39.7%) and peripheral vascular disease (21.7%). The average hemoglobin was 9.3 ± 1.3. The case-mix adjusted center effect accounted for 20% of variance in Qsub. The top 10 most important variables associated with higher Qsub were effective Qb, serum protein, Charlson's comorbidity index, hemoglobin, year of dialysis initiation (proxy of high Qsub treatment policy in the clinic network), predialysis heart rate, serum bicarbonate, serum phosphate, age, serum sodium, and dry body weight. In addition, we found that the association of Qb with Qsub is moderated by year of enrollment, intradialytic weight gain, and coronary artery disease, whereas higher hemoglobin concentration moderated the relationship between treatment time and Qsub. Finally, Qsub between 21 and 25 L/session was associated with longer 5-year survival. CONCLUSIONS: Both center-dependent clinical practice standards and patient clinical conditions substantially contributed to the risk of low Qsub. We confirmed previous evidence indicating better survival among patients with Qsub ≥ 21 L/session.