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.

Determination of dialysis dose: a clinical comparison of methods.

BACKGROUND: Guidelines recommend regular measurements of the delivered hemodialysis dose Kt/V. Nowadays, automatic non-invasive online measurements are available as alternatives to the conventional method with blood sampling, laboratory analysis, and calculation. METHODS: In a prospective clinical trial, three different methods determining dialysis dose were simultaneously applied: Kt/V(Dau) (conventional method with Daugirdas' formula), Kt/V(OCM) [online clearance measurement (OCM) with urea distribution volume V based on anthropometric estimate], and Kt/V(BCM) [OCM measurement with V measured by bioimpedance analysis (Body Composition Monitor)]. RESULTS: 1,076 hemodialysis patients were analyzed. The dialysis dose was measured as Kt/V(Dau) = 1.74 ± 0.45, Kt/V(OCM) = 1.47 ± 0.34, and Kt/V(BCM) = 1.65 ± 0.42. The difference between Kt/V(OCM) and Kt/V(BCM) was due to the difference between anthropometric estimated V(Watson) and measured V(BCM). Compared to Kt/V(Dau), Kt/V(OCM) was 15% lower and Kt/V(BCM) 5% lower. Kt/V(Dau) was incidentally prone to falsely high values due to operative errors, whereas in these cases OCM-based measurements Kt/V(OCM) and Kt/V(BCM) delivered realistic values. CONCLUSIONS: The automated OCM Kt/V(OCM) with anthropometric estimation of urea distribution volume was the easiest method to use, but Kt/V(BCM) with measured urea distribution volume was closer to the conventional method.

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.

Improved intradialytic stability during haemodialysis with blood volume-controlled ultrafiltration.

BACKGROUND: Intradialytic morbid events (IMEs) during haemodialysis (HD), including symptomatic hypotension, are related to ultrafiltration (UF)-induced hypovolaemia. Blood volume monitoring and automatic feedback control of the UF rate were developed to limit the extent of hypovolaemia during dialysis. The present study investigated the effect of blood volume (BV)-controlled UF on the incidence of HD treatments with IMEs. METHODS: This prospective randomised crossover study included hypotension-prone patients, characterised by occurrence of IMEs in at least 33% of HD treatments during a 6-week screening phase. These patients underwent 2 treatment phases, each lasting 6 weeks, in randomised order. Each patient served as their own control, treated with standard HD in one phase and with BV-controlled UF in the other phase. RESULTS: Thirty-four patients from 9 HD centres were enrolled; 26 could be included in the analysis population. In comparison with standard HD, BV-controlled UF reduced the percentage of HD sessions complicated by IME significantly from 40%+/-27% to 32%+/-25% (p=0.02). A lower frequency of HD sessions with IME could be observed in 46% of the patients. The frequency of treatments with symptomatic hypotension was reduced from 32%+/-23% in standard HD to 24%+/-21% with BV-controlled UF (p=0.04). Changes in blood pressure and heart rate from start to end of the HD session were not different between the 2 treatment modes. CONCLUSIONS: This crossover study showed improved intradialytic stability with BV-controlled UF, compared with standard HD.

Observation of microbubbles during standard dialysis treatments.

BACKGROUND: The infusion of microbubbles as a side effect of haemodialysis was repeatedly demonstrated in recent publications, but the knowledge on the source of microbubbles and on microbubble formation is scarce. METHODS: Microbubbles in the range of 10-500 µm were measured by a non-invasive bubble counter based on a pulsed ultrasonic Doppler system in a non-interventional study of a single centre. Totally, 29 measurements were performed in standard treatments covering a broad range of patient and treatment conditions (types of blood access, treatment modes, blood flow rates and arterial pressures). RESULTS: Several possible sources of microbubbles could be identified such as an arterial luer lock connector at negative pressure and remnant bubbles from insufficient priming, but some sources of microbubbles remain unknown. Microbubbles were found in all treatments, haemodialysis (HD) and online haemodiafiltration. The lowest average microbubble rates (17 ± 16 microbubbles per minute) were observed in patients treated by online haemodiafiltration at medium blood flow rates and moderate arterial pressures and the highest average microbubble rates (117 ± 63 microbubbles per minute) at high blood flow rates (550 mL/min) and low arterial pressures (-210 mmHg). Generally, the microbubble rate correlated to both blood flow rate (correlation coefficient r = 0.45) and negative arterial pressure (r = 0.67). CONCLUSIONS: Microbubbles are a general side effect of HD; origin and pathophysiologic consequences of this phenomenon are not well understood, and deserve further study.

Simultaneous blood temperature control and blood volume control reduces intradialytic symptoms.

PURPOSE: Intra-dialytic morbid events (IME; e.g. hypotension, cramps, headaches) are frequent complications during hemodialysis (HD), known to be associated with ultrafiltration-induced hypovolemia and body temperature changes. Feedback control of blood volume adjusts the ultrafiltration rate in order to keep the blood volume above the patient's individual limit; feedback control of blood temperature maintains the mean arterial blood temperature at the individual pre-dialytic level. Each of these methods reduces the frequency of IME. METHODS: In a randomized clinical trial the simultaneous application of both feedback controls was investigated for the first time. In 15 weeks, each patient went through 3 study phases: an observational screening phase, a standard phase (STD), and a blood temperature- and blood volume-control phase (CTL). Patients with at least 5 sessions with IME out of 15 sessions in the screening phase were eligible for the study and randomized either into sequence STD-CTL or CTL-STD. RESULTS: 26 patients completed the study according to protocol, and 778 HD treatments were analyzed. The general treatment parameters were similar in both study phases: treatment duration (STD: 244 min, CTL: 243 min, NS), pre-dialytic weight (STD: 72.3 kg, CTL: 72.2 kg, NS), and weight loss due to ultrafiltration (STD: 3.26 kg, CTL: 3.15 kg, NS). The proportion of HD treatments with IME was 32.8% during STD and 18.0% during CTL (p=0.024). CONCLUSIONS: The frequency of HD sessions with IME was significantly reduced by 45% compared to standard HD in this randomized clinical trial by use of individualized HD treatments with simultaneous feedback control of blood volume and blood temperature.

Dialysate saving by automated control of flow rates: comparison between individualized online hemodiafiltration and standard hemodialysis.

Cost reduction and quality improvement seem to be conflicting issues. However, online hemodiafiltration (oHDF) with new automatic functions offers a cost-efficient therapy compared to hemodialysis (HD). Seven dialysis centers conducted a randomized clinical trial with cross-over design: high-flux HD vs. postdilutional oHDF with functions coupling both dialysate and substitution flow rates to blood flow rates. During the 6 weeks of the study, all treatment parameters remained unchanged for HD and oHDF, apart from dialysate and substitution flow rate. Treatment data were recorded during each treatment, and predialytic and postdialytic concentrations of urea were recorded at the end of each study phase. The analysis involved 956 treatments of 54 patients. The mean dialysate consumption was 123.2 ± 6.4 l for HD and 113.4 ± 14.9 l for oHDF (p < 0.0001), the mean dialysis dose was 1.42 ± 0.23 for HD and 1.47 ± 0.26 for oHDF (p < 0.0001); oHDF resulted in a lower dialysate consumption (8.0% less) and a slightly increased dialysis dose (Kt/V 3.5% higher) compared to HD. oHDF with the investigated automatic functions offers substantial savings in dialysate consumption without decreasing dialysis dose.

On-line haemodiafiltration versus haemodialysis: stable haematocrit with less erythropoietin and improvement of other relevant blood parameters.

BACKGROUND: Controlled randomised studies to prove improved cardiovascular stability and improved anaemia management during on-line haemodiafiltration (oHDF) are scarce. METHODS: 70 patients were treated with both haemodialysis (HD) and oHDF in a cross-over design during 2 x 24 weeks at a dialysis dose of eKt/V> or =1.2. Patients randomised into group A started on HD and switched over to oHDF, whereas patients in group B began with oHDF and were treated with HD afterwards. Intradialytic morbid events (IME), such as symptomatic hypotension or muscle cramps, were noted in case of appearance. Blood parameters reflecting anaemic status, phosphate status, lipid metabolism, oxidative stress, and accumulation of advanced glycation end products were recorded either monthly or at the end of each study phase. RESULTS: The mean incidence of IME was 0.15 IME per treatment, and there was no statistical difference between oHDF and HD. A higher haematocrit (oHDF 31.5% vs. HD 30.5%, p < 0.01) at a lower erythropoietin dose (oHDF 4,913 vs. HD 5,492 IU/week, p = 0.02) was found during oHDF, when the sequence of HD and oHDF had not been taken into account. For the study groups, the results were less distinct: in group A, a higher haematocrit (HD 30.4% vs. oHDF 32.0%, p < 0.01) at a comparable erythropoietin dose (HD 5,421 vs. oHDF 5,187 IU/week, ns) was observed during oHDF, whereas in group B an identical haematocrit (oHDF 30.8% vs. HD 30.7%, ns) was achieved at a reduced erythropoietin dose (oHDF 4,622 vs. HD 5,568 IU/week, p < 0.01). During oHDF, lower levels of free and protein-bound pentosidine and of serum phosphate were found. CONCLUSION: In contrast to other studies, no benefit regarding cardiovascular stability for oHDF was found, but oHDF could well offer a potential benefit regarding anaemia correction, inflammation, oxidative stress, lipid profiles, and calcium-phosphate product.

On-line hemodiafiltration does not induce inflammatory response in end-stage renal disease patients: results from a multicenter cross-over study.

BACKGROUND: On-line hemodiafiltration (HDF) represents the supreme blood purification modality for end-stage renal disease (ESRD) patients. Large-volume infusion of on-line prepared substitution fluid may, however, expose patients to inflammatory contaminants. As a result, on-line HDF might aggravate chronic inflammation, which correlates with malnutrition, cardiovascular disease, and mortality among ESRD patients. METHODS: In a multicenter cross-over study, 27 ESRD patients were randomly assigned to treatment with on-line HDF and low-flux hemodialysis (HD). After 6 months, patients were crossed to the other treatment modality, and treatment continued for another 6 months. Both on-line HDF and low-flux HD were conducted with polysulfone membranes and ultrapure dialysis fluid. Samples were drawn at the end of each treatment period. RESULTS: Inflammatory parameters were elevated in the study population when compared to healthy controls. Induction of interleukin-1 receptor antagonist (IL-1Ra) and tumor necrosis factor alpha (TNF-alpha) was comparable for on-line HDF and low-flux HD, and there was no intradialytic increase in cytokine production. As a result, interleukin-6 (IL-6) plasma levels did not differ significantly between the two treatment modalities. Similarly, no difference between on-line HDF and low-flux HD was observed for C-reactive protein (CRP) and albumin. Markers of endothelial cell activation (soluble intercellular and vascular cell adhesion molecules sICAM-1 and sVCAM-1) as well as the cardiovascular risk marker cardiac troponin T (cTnT) remained elevated compared to healthy subjects, but showed no difference between the two treatment modalities. CONCLUSIONS: On-line HDF, as the most effective renal replacement therapy, does not provoke inflammatory response and is both safe and highly biocompatible.

Characteristics of hypotension-prone haemodialysis patients: is there a critical relative blood volume?

BACKGROUND: Intradialytic morbid events (IME, mostly hypotension) mainly due to ultrafiltration-induced hypovolaemia still are the most frequent complication during haemodialysis (HD). This study was performed to test the hypothesis that there is an individual critical relative blood volume (RBV(crit)) in IME-prone HD patients. METHODS: In this prospective international multicentre study, 60 IME-prone patients from nine dialysis centres were observed during up to 21 standard HD sessions without trial-specific intervention. The RBV was monitored continuously by an ultrasonic method (BVM; blood volume monitor). Also, the ultrafiltration rate was registered continuously. Blood pressure was measured at regular intervals, and more frequently during IME. All IME and specific therapeutic interventions were noted. RESULTS: In total, 537 IME, some with more than one symptom, were documented during 585 HD sessions. The occurrence of IME increased up to 10-fold from the start to the end of the HD session. RBV(crit) showed a wide inter-individual range, varying from 71 to 98%. However, the intra-individual RBV limit was relatively stable, with an SD of <5% in three-quarters of the patients. In patients with congestive heart failure, cardiac arrhythmia, advanced age, low ultrafiltration volume and low diastolic blood pressure, higher values of RBV(crit) were observed. While all correlations between RBV(crit) and patient characteristics alone were found to be of weak or medium strength, the combination of diastolic blood pressure, ultrafiltration volume and age resulted in a strong correlation with RBV(crit): the linear equation with these parameters allows an estimation of RBV(crit) in patients not yet monitored with a BVM. CONCLUSIONS: An individual RBV limit exists for nearly all patients. In most IME-prone patients, these RBV values were stable with only narrow variability, thus making it a useful indicator to mark the individual window of haemodynamic instabilities.