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.

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.

Ionic dialysance measurement is urea distribution volume dependent: a new approach to better results.

Conductivity (CD)-based dialysance measurements precisely match urea dialysance with <5% difference. For measurement, a CD step-profile is applied by increasing dialysate inlet CD at time t0 for 10% above baseline and lasting for 2-5 min until t1, followed by a decrease to -4% until t2 and a final return to baseline, meanwhile recording dialysate CD at filter inlet (cdi) and outlet (cdo), dialysate flow (Qd), and ultrafiltration (UF)-rate (Qf). Electrolytic dialysance (KeCn) is calculated by KeCnI,J = (1 -[cdoI-cdoJ]/[cdiI-cdiJ])(Qd+Qf) with time index I not = J. The combinations in I,J are not equivalent: KeCn0,1 < KeCn1,2 < KeCn0,2. Each difference is 2% to 5%, and a difference versus urea clearance remains. An in vivo on-line clearance study (10 patients, 100 dialysis sessions, 265 measurements) with automatic electrolytical dialysance measurements and permanent data recording was conducted. Two methods were applied: a CD step-profile and a significantly smaller, dynamic CD bolus. Both were compared to laboratory reference of urea clearance. Reference Kt/V has been calculated using equilibrated single-pool methods and direct quantification. Urea generation was ignored. The results are as follows. The reference blood-side urea clearance was 164.0 +/- 11.8 ml/min, n = 265. The mean errors of the ionic dialysance results are KeCn0,1: -9.1 +/- 4.8%, n = 250; KeCn1,2: -5.6 +/- 4.4%, n = 250; KeCn0,2: 6.8 +/- 7.7%, n = 250; KeCnBolus: 0.1 +/- 4.8%, n = 162. The KeCnI,J error is urea distribution volume related. Kt/V comparison to equilibrated single pool is as follows: KeCn1,2t/V: 0.0 +/- 5.0% (r = 0.96, n = 45); KeCnBolust/V: 5.3 +/- 3.9% (r = 0.98, n = 44). The comparison to direct quantification is as follows: KeCn1,2t/V: -2 +/- 6.4% (r = 0.95, n = 68); KeCnBolust/V: 3.2 +/- 6.3% (r = 0.95, n = 66). V could roughly be measured. Dialysance measured by the step-function method was dependent on sodium load and distribution volume while the CD-bolus dialysance was not. Errors are generated by measurement-induced sodium shift that is sufficient even to estimate urea distribution volume. For dialysance measurements, small dynamic CD boli are preferable to stable step functions.