Does online high-volume hemodiafiltration offer greater efficiency and sustainability compared with high-flux hemodialysis? A detailed simulation analysis anchored in real-world data.

Recent findings, including the CONVINCE (comparison of high-dose HDF with high-flux HD) study report, suggest the superiority of high-volume hemodiafiltration (HDF) over high-flux hemodialysis (HD) in improving patients' outcomes. Despite positive patient outcomes, concerns have arisen about the potential negative environmental impact of high-volume HDF, as it may lead to increased water and dialysis fluid consumption and higher waste production. In this manuscript, we address the environmental impact of high-volume HDF, focusing on three key factors: water treatment consumption, dialysis fluid consumption, and solute efficiency markers of HD and HDF. By optimizing HDF prescription through adjustments in operational capabilities, while keeping a high blood flow (i.e., >350 ml/min) such as reducing the QD/QB ratio to 1.2 rather than 1.4 or 1.5 and incorporating automated ultrafiltration and substitution control, we demonstrate that HDF delivers a higher dialysis dose for small- and middle-molecule uremic compounds with the same dialysis fluid consumption, and at equal dialysis doses dialysis fluid consumption is reduced. This finding is supported by real-world data from 26 031 patients who underwent high-volume postdilution HDF at a reduced dialysis flow (430 mL/min) and achieved an effective OCMKt/V of 1.70 (where "OCM" stands for online clearance measurement, "K" represents effective dialysis clearance and "V" denotes total body water measured by multifrequency bioimpedance). In addition, simulation modeling calculations, using blood extraction coefficient, dialysate saturation coefficient and solute clearances with urea (small molecular weight) and ß2-microglobulin (middle molecular weight), consistently show the superiority of postdilution HDF to HD. This holds true even with a significant reduction in dialysis flow down to 430 mL/min, reflecting QD/QB ratio of 1.2. Postdilution HDF generates high ultrafiltrate flow (up to 35% of blood flow), delivering saturated ultrafiltrate to the lower solute concentration containing effluent dialysate, thus enhancing solute clearance which opens the way to reduce the dialysis flow. In conclusion, our analysis, combining simulation and real-world data, suggests that postdilution HDF could be a more environmentally friendly treatment option compared with conventional HD. Additionally, automated user-friendly functions that minimize dialysis fluid use can further strengthen this environmental benefit while enhancing efficiency.

Detection of Hyponatremia Development in Hemodialysis Patients by Routine Automated Conductivity-Based Monitoring.

Predialytic hyponatremia is associated with poor outcome in hemodialysis patients. Hypotonic hyponatremia is the most frequently encountered disorder reflecting mixed disorders combining extracellular fluid overload and free water excess, resulting from the interplay of intermittency of dialysis and diet observance, and likely precipitated by an acute or subacute illness. In this context, hyponatremia requires to be detected and worked up to identify and cure the cause. In this clinical case report, we describe preliminary results of using an online biosensor on a dialysis machine that provides automated predialysis plasma sodium concentration derived from dialysate conductivity measurements. Based on this biosensor, within a 5 year time frame, 11 patients out of more than 130 maintenance hemodialysis patients and over 40,000 dialysis sessions were identified with episodes of predialysis hyponatremia (≤135 mmol/l). In all patients, hyponatremic episodes were indicative of a severe underlying illness associated with fluid overload leading to plasma hypotonicity. Automated online predialysis plasma sodium concentration measurement offers an innovative, reliable, and cost-free tool that permits to detect hyponatremia as marker of an underlying illness development in dialysis patients. The value of this tool in supporting clinical decision-making deserves further studies in a large dialysis population.

Hidden risks associated with conventional short intermittent hemodialysis: A call for action to mitigate cardiovascular risk and morbidity.

The development of maintenance hemodialysis (HD) for end stage kidney disease patients is a success story that continues to save many lives. Nevertheless, intermittent renal replacement therapy is also a source of recurrent stress for patients. Conventional thrice weekly short HD is an imperfect treatment that only partially corrects uremic abnormalities, increases cardiovascular risk, and exacerbates disease burden. Altering cycles of fluid loading associated with cardiac stretching (interdialytic phase) and then fluid unloading (intradialytic phase) likely contribute to cardiac and vascular damage. This unphysiologic treatment profile combined with cyclic disturbances including osmotic and electrolytic shifts may contribute to morbidity in dialysis patients and augment the health burden of treatment. As such, HD patients are exposed to multiple stressors including cardiocirculatory, inflammatory, biologic, hypoxemic, and nutritional. This cascade of events can be termed the dialysis stress storm and sickness syndrome. Mitigating cardiovascular risk and morbidity associated with conventional intermittent HD appears to be a priority for improving patient experience and reducing disease burden. In this in-depth review, we summarize the hidden effects of intermittent HD therapy, and call for action to improve delivered HD and develop treatment schedules that are better tolerated and associated with fewer adverse effects.

Sodium First Approach, to Reset Our Mind for Improving Management of Sodium, Water, Volume and Pressure in Hemodialysis Patients, and to Reduce Cardiovascular Burden and Improve Outcomes.

New physiologic findings related to sodium homeostasis and pathophysiologic associations require a new vision for sodium, fluid and blood pressure management in dialysis-dependent chronic kidney disease patients. The traditional dry weight probing approach that has prevailed for many years must be reviewed in light of these findings and enriched by availability of new tools for monitoring and handling sodium and water imbalances. A comprehensive and integrated approach is needed to improve further cardiac health in hemodialysis (HD) patients. Adequate management of sodium, water, volume and hemodynamic control of HD patients relies on a stepwise approach: the first entails assessment and monitoring of fluid status and relies on clinical judgement supported by specific tools that are online embedded in the HD machine or devices used offline; the second consists of acting on correcting fluid imbalance mainly through dialysis prescription (treatment time, active tools embedded on HD machine) but also on guidance related to diet and thirst management; the third consist of fine tuning treatment prescription to patient responses and tolerance with the support of innovative tools such as artificial intelligence and remote pervasive health trackers. It is time to come back to sodium and water imbalance as the root cause of the problem and not to act primarily on their consequences (fluid overload, hypertension) or organ damage (heart; atherosclerosis, brain). We know the problem and have the tools to assess and manage in a more precise way sodium and fluid in HD patients. We strongly call for a sodium first approach to reduce disease burden and improve cardiac health in dialysis-dependent chronic kidney disease patients.

Dialysis-Induced Cardiovascular and Multiorgan Morbidity.

Hemodialysis has saved many lives, albeit with significant residual mortality. Although poor outcomes may reflect advanced age and comorbid conditions, hemodialysis per se may harm patients, contributing to morbidity and perhaps mortality. Systemic circulatory "stress" resulting from hemodialysis treatment schedule may act as a disease modifier, resulting in a multiorgan injury superimposed on preexistent comorbidities. New functional intradialytic imaging (i.e., echocardiography, cardiac magnetic resonance imaging [MRI]) and kinetic of specific cardiac biomarkers (i.e., Troponin I) have clearly documented this additional source of end-organ damage. In this context, several factors resulting from patient-hemodialysis interaction and/or patient management have been identified. Intradialytic hypovolemia, hypotensive episodes, hypoxemia, solutes, and electrolyte fluxes as well as cardiac arrhythmias are among the contributing factors to systemic circulatory stress that are induced by hemodialysis. Additionally, these factors contribute to patients' symptom burden, impair cognitive function, and finally have a negative impact on patients' perception and quality of life. In this review, we summarize the adverse systemic effects of current intermittent hemodialysis therapy, their pathophysiologic consequences, review the evidence for interventions that are cardioprotective, and explore new approaches that may further reduce the systemic burden of hemodialysis. These include improved biocompatible materials, smart dialysis machines that automatically may control the fluxes of solutes and electrolytes, volume and hemodynamic control, health trackers, and potentially disruptive technologies facilitating a more personalized medicine approach.

Evaluation of intradialytic sodium shifts during sodium controlled hemodialysis.

Plasma sodium shifts during hemodialysis treatments can be minimized by application of a sodium control algorithm. The present randomized cross-over trial was designed to apply this option on a large patient cohort and to observe the time course of plasma sodium over the treatment. In one study phase, patients received post-dilution online hemodiafiltration treatments with sodium control over the entire treatment. In the other study phase, patients received isolated ultrafiltration during the first 90 min followed by post-dilution online hemodiafiltration with sodium control for the remainder of the session, with the purpose to follow a possible initial equilibration process without the influence of a diffusive solute transfer. Each phase included six treatments and was delivered in randomized order. Eighty-one patients were enrolled, 77 patients could be analyzed as intention-to-treat population. The difference of the mean plasma sodium concentration between start and end of the treatment was -0.60 mmol/L (confidence interval -0.88 to -0.32) and -0.15 mmol/L (confidence interval -0.43 to 0.13), for sodium control and isolated ultrafiltration during the first 90 min followed by post-dilution online hemodiafiltration with sodium control, respectively. The functionality of the sodium control option could be confirmed and further reproduced in a bigger population of dialysis patients, providing the basis to investigate the clinical benefit of individually adjusting dialysate sodium in further clinical studies.

Automated individualization of dialysate sodium concentration reduces intradialytic plasma sodium changes in hemodialysis.

In standard care, hemodialysis patients are often treated with a center-specific fixed dialysate sodium concentration, potentially resulting in diffusive sodium changes for patients with plasma sodium concentrations below or above this level. While diffusive sodium load may be associated with thirst and higher interdialytic weight gain, excessive diffusive sodium removal may cause intradialytic symptoms. In contrast, the new hemodialysis machine option "Na control" provides automated individualization of dialysate sodium during treatment with the aim to reduce such intradialytic sodium changes without the need to determine the plasma sodium concentration. This proof-of-principle study on sodium control was designed as a monocentric randomized controlled crossover trial: 32 patients with residual diuresis of ≤1000 mL/day were enrolled to be treated by high-volume post-dilution hemodiafiltration (HDF) for 2 weeks each with "Na control" (individually and automatically adjusted dialysate sodium concentration) versus "standard fixed Na" (fixed dialysate sodium 138 mmol/L), in randomized order. Pre- and post-dialytic plasma sodium concentrations were determined at bedside by direct potentiometry. The study hypothesis consisted of 2 components: the mean plasma sodium change between the start and end of the treatment being within ±1.0 mmol/L for sodium-controlled treatments, and a lower variability of the plasma sodium changes for "Na control" than for "standard fixed Na" treatments. Three hundred seventy-two treatments of 31 adult chronic hemodialysis patients (intention-to-treat population) were analyzed. The estimate for the mean plasma sodium change was -0.53 mmol/L (95% confidence interval: [-1.04; -0.02] mmol/L) for "Na control" treatments and -0.95 mmol/L (95% CI: [-1.76; -0.15] mmol/L) for "standard fixed Na" treatments. The standard deviation of the plasma sodium changes was 1.39 mmol/L for "Na control" versus 2.19 mmol/L for "standard fixed Na" treatments (P = 0.0004). Whereas the 95% CI for the estimate for the mean plasma sodium change during "Na control" treatments marginally overlapped the lower border of the predefined margin ±1.0 mmol/L, the variability of intradialytic plasma sodium changes was lower during "Na control" versus "standard fixed Na" treatments. Thus, automated dialysate sodium individualization by "Na control" approaches isonatremic dialysis in the clinical setting.

Sodium and water handling during hemodialysis: new pathophysiologic insights and management approaches for improving outcomes in end-stage kidney disease.

Space medicine and new technology such as magnetic resonance imaging of tissue sodium stores (23NaMRI) have changed our understanding of human sodium homeostasis and pathophysiology. It has become evident that body sodium comprises 3 main components. Two compartments have been traditionally recognized, namely one that is circulating and systemically active via its osmotic action, and one slowly exchangeable pool located in the bones. The third, recently described pool represents sodium stored in skin and muscle interstitium, and it is implicated in cell and biologic activities via local hypertonicity and sodium clearance mechanisms. This in-depth review provides a comprehensive view on the pathophysiology and existing knowledge gaps of systemic hemodynamic and tissue sodium accumulation in dialysis patients. Furthermore, we discuss how the combination of novel technologies to quantitate tissue salt accumulation (e.g., 23NaMRI) with devices to facilitate the precise attainment of a prescribed hemodialytic sodium mass balance (e.g., sodium and water balancing modules) will improve our therapeutic approach to sodium management in dialysis patients. While prospective studies are required, we think that these new diagnostic and sodium balancing tools will enhance our ability to pursue more personalized therapeutic interventions on sodium and water management, with the eventual goal of improving dialysis patient outcomes.

Zero Diffusive Sodium Balance in Hemodialysis Provided by an Algorithm-Based Electrolyte Balancing Controller: A Proof of Principle Clinical Study.

Restoring and controlling fluid volume homeostasis is still a challenge in contemporary end-stage kidney disease patients treated by intermittent hemodialysis (HD) or hemodiafiltration (HDF). This primary target is achieved by ultrafiltration (dry weight probing) and control of intradialytic sodium transfer (dialysate-plasma Na gradient). The latter task is mostly ignored in clinical practice by applying a dialysate sodium prescription uniform for all patients of the dialysis center but unaligned to individual plasma sodium levels. Depending on the patient's natremia, a positive gradient gives rise to intradialytic diffusive sodium load and postdialytic thirst. On the contrary, a negative gradient may cause unwanted diffusive sodium removal and intradialytic symptoms. To overcome these challenges, a new conductivity-based electrolyte balancing algorithm embedded in a hemodialysis machine with the aim to achieve "zero diffusive sodium balance" in HD and online HDF treatments was tested in the form of a prospective clinical trial. The study comprised two phases: a first phase with a conventional fixed-sodium dialysate (standard care phase), followed by a phase with the electrolyte balancing control (EBC) module activated (controlled care phase). The results show a reduction in the variability of the intradialytic plasma sodium concentration shift, but it is overlain by a small but statistically significant increase in the mean plasma sodium levels. However, no clinical manifestations were observed. This sodium load can be explained by the design of the algorithm based on dialysate conductivity instead of sodium concentration. Furthermore, the increase in plasma sodium can be corrected by taking into account the potassium shift during the treatment. This study showed that the EBC module incorporated in the HD machine is able to automatically individualize the dialysate sodium to the patient's plasma sodium without measuring or calculating predialytic plasma levels from previous laboratory tests. This tool has the potential to facilitate fluid management, to control diffusive sodium flux, and to improve intradialytic tolerance in daily clinical practice.