How biocompatible haemodialysers can conquer the need for systemic anticoagulation even in post-dilution haemodiafiltration: a cross-over study.

BACKGROUND: While systemic anticoagulation is most widely used in haemodialysis (HD), contraindications to its use might occur in particular settings. The Solacea™ haemodialyser with an asymmetric triacetate membrane claims improved biocompatibility and has already shown promising results when used in combination with only half dose of anticoagulation. To quantify the performance of the Solacea™ when further decreasing anticoagulation to zero, fibre blocking was assessed by micro-computed tomography (micro-CT). METHODS: Ten maintenance HD patients underwent six dialysis sessions at midweek using a Solacea™ 19H dialyser, consecutively in pre-dilution haemodiafiltration (pre-HDF), HD and post-dilution HDF (post-HDF). After the first three sessions with only a quarter of their regular anticoagulation dose (one-quarter), the last three sessions were performed without anticoagulation (zero). Dialyser fibre blocking was quantified in the dialyser outlet potting using a 3D micro-CT scanning technique post-dialysis. RESULTS: Even in case of reduced (one-quarter) anticoagulation, the relative number of open fibres post-dialysis was almost optimal, i.e. 0.96 (0.87-0.99) with pre-HDF, 0.99 (0.97-0.99) with HD and 0.97 (0.92-0.99) with post-HDF. Fibre patency was mildly decreased for pre-HDF and HD when anticoagulation was decreased from one-quarter to zero, i.e. to 0.76 (0.61-0.85) with pre-HDF (P = 0.004) and to 0.80 (0.77-0.89) with HD (P = 0.013). Comparing the results for zero anticoagulation, post-HDF [i.e. 0.94 (0.82-0.97)] performed as well as HD and pre-HDF. CONCLUSIONS: The Solacea™ dialyser provides promising results for use in conditions where systemic anticoagulation is contraindicated. Post-HDF, although inducing haemoconcentration in the dialyser, is equally effective for fibre patency in case of zero anticoagulation as pre-HDF and HD when using Solacea™.

Erratum: A randomized cross-over study with objective quantification of the performance of an asymmetric triacetate and a polysulfone dialysis membrane using different anticoagulation strategies.

[This corrects the article DOI: 10.1093/ckj/sfz163.][This corrects the article DOI: 10.1093/ckj/sfz163.].

A randomized cross-over study with objective quantification of the performance of an asymmetric triacetate and a polysulfone dialysis membrane using different anticoagulation strategies.

BACKGROUND: Different strategies can be used to counteract coagulation of extracorporeal systems. Systemic anticoagulation is most widely used in routine clinical practice, but can be contraindicated in specific settings. The Solacea™ dialyser, containing the asymmetric triacetate membrane, claims improved biocompatibility, which should result in decreased tendency for coagulation. We quantified the performance of the Solacea™ versus the FX800CORDIAX dialyser regarding resistance to fibre blocking as assessed by micro-computed tomography (CT). METHODS: This cross-over study with four arms randomized consecutively 10 maintenance haemodialysis patients to a 4-h post-dilution haemodiafiltration session at midweek, using either Solacea™ 19 H or FX800CORDIAX, with either regular or half dose of anticoagulation (EC2017/1459-NCT03820401). Dialyser fibre blocking was visualized in the dialyser outlet potting using a 3D CT scanning technique on micrometre resolution. Extraction ratios of middle molecules [myoglobin, lambda and kappa free light chains (FLCs)] were determined. RESULTS: The relative number of open fibres post-dialysis was lower in FX800CORDIAX versus Solacea™ dialyser, and this was irrespective of the anticoagulation dose used or the threshold for counting open fibres. Extraction ratios of FLCs were not different at regular anticoagulation between Solacea™ and FX800CORDIAX (21% ± 4% for kappa and 32% ± 8% for lambda with Solacea™ versus 23% ± 7% and 38% ± 6% for FX800CORDIAX), but were superior with the Solacea™ (34% ± 12% versus 22% ± 8% with FX800CORDIAX; P = 0.02) for myoglobin in case of halving anticoagulation dose. No clinically relevant albumin loss was detected. CONCLUSIONS: The Solacea™ dialyser seems to be promising for use in conditions where systemic anticoagulation is contraindicated, as even under conditions of low systemic anticoagulation, virtually no signs of fibre blocking could be observed using the sensitive micro-CT scanning technique. This finding is in line with its presumed good performance in terms of biocompatibility.

Urokinase-containing locking solution in the prevention of dialysis catheter dysfunction: a double blind randomized controlled trial.

INTRODUCTION: The prophylactic use of recombinant tissue plasminogen activator once weekly reduces the incidence rate of tunneled cuffed catheter (TCC) malfunction and bacteremia as compared to the exclusive use of heparin as locking solution. Restricting the use of prophylactic thrombolytic agents to patients with a history of thrombotic TCC malfunction could be more cost effective. We conduct a multicenter, double-blind, randomized controlled trial and test the hypothesis that weekly use of urokinase lock will reduce the incidence of thrombotic malfunction by 50% in prevalent hemodialysis patients with a history of thrombotic malfunction. METHODS: Patients with a history of at least two separate TCC thrombotic dysfunctions treated with urokinase lock during the 6 months preceding inclusion are recruited in eight Belgian dialysis units. Patients are randomized in two groups: the control group receiving Taurolock™-HEP500 (heparin 500 IU/mL, taurolidine, citrate 4%) after each hemodialysis session and the treatment group receiving Taurolock-U 25,000 (urokinase 25,000, taurolidine, citrate 4%) once a week and the standard Taurolock-HEP500 at the end of the two others sessions. The primary outcome is the incidence rate of TCC thrombotic dysfunction defined by the use of urokinase. The secondary outcomes are the incidence rate of TCC removal and systemic thrombolysis. For the study, both patients and healthcare staff are blinded to treatment allocation. CONCLUSIONS: The present trial is the first to investigate the effect of Taurolock-U 25,000 catheter lock once a week as secondary prevention in hemodialysis patients with the highest risk of TCC-related thrombotic dysfunction. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036255.

Protein-Bound Uremic Toxin Profiling as a Tool to Optimize Hemodialysis.

AIM: We studied various hemodialysis strategies for the removal of protein-bound solutes, which are associated with cardiovascular damage. METHODS: This study included 10 patients on standard (3 x 4 h/week) high-flux hemodialysis. Blood was collected at the dialyzer inlet and outlet at several time points during a midweek session. Total and free concentration of several protein-bound solutes was determined as well as urea concentration. Per solute, a two-compartment kinetic model was fitted to the measured concentrations, estimating plasmatic volume (V1), total distribution volume (V tot) and intercompartment clearance (K21). This calibrated model was then used to calculate which hemodialysis strategy offers optimal removal. Our own in vivo data, with the strategy variables entered into the mathematical simulations, was then validated against independent data from two other clinical studies. RESULTS: Dialyzer clearance K, V1 and V tot correlated inversely with percentage of protein binding. All Ks were different from each other. Of all protein-bound solutes, K21 was 2.7-5.3 times lower than that of urea. Longer and/or more frequent dialysis that processed the same amount of blood per week as standard 3 x 4 h dialysis at 300 mL/min blood flow showed no difference in removal of strongly bound solutes. However, longer and/or more frequent dialysis strategies that processed more blood per week than standard dialysis were markedly more adequate. These conclusions were successfully validated. CONCLUSION: When blood and dialysate flow per unit of time and type of hemodialyzer are kept the same, increasing the amount of processed blood per week by increasing frequency and/or duration of the sessions distinctly increases removal.

Association of advanced age with concentrations of uraemic toxins in CKD.

To our knowledge, there are no studies on advanced chronic kidney disease (CKD) analysing the impact of ageing on serum concentrations of uraemic toxins while adjusting for renal function. Knowledge of this feature, however, could influence prognostic assessment and therapeutic decision-making, e.g. about when to start dialysis or how intensive it should be. Indeed, the slowing down of metabolism with age may result in lower uraemic toxin concentrations, hence reducing their toxic effects. In this case, a later start of dialysis or less intensive dialysis may become justified in an already fragile population that might enjoy a better quality of life without a survival disadvantage with conservative treatment. We assessed the impact of advancing age on uraemic solute concentrations [blood, urea, nitrogen (BUN), uric acid, creatinine, asymmetric and symmetric dimethylarginine (ADMA and SDMA), ß2-microglobulin and a large array of protein-bound solutes] by matching 126 maintenance haemodialysis patients subdivided into two age-groups, younger vs. older (using the median as cut-off: 72 years). Concentrations were compared after age stratification and were matched with patient and dialysis characteristics. In addition, 93 non-dialysed CKD patients (median as cut-off: 70 years), with a comparable average estimated glomerular filtration rate (eGFR) between younger and older age-groups, were analysed. In haemodialysis patients, carboxy-methyl-furanpropionic acid (CMPF) levels were markedly higher and BUN and uric acid borderline lower in the older age-group. All other solutes showed no difference. At multifactor analysis, the concentration of several uraemic toxins was associated with residual renal function and protein intake in the overall haemodialysis group and the younger group, but the association with most solutes, especially those protein-bound, was lost in the older age-group. No differences were found in non-dialysed CKD patients. It was concluded that in this CKD population concentrations of uraemic toxins did not change substantially with calendar age.

The relationship of NT-proBNP and dialysis parameters with outcome of incident haemodialysis patients: results from the membrane permeability outcome study.

BACKGROUND/AIMS: The association of raised levels of natriuretic peptides with elevated risk of mortality was investigated in the present analysis of the Membrane Permeability Outcome study. METHODS: N-terminal probrain type natriuretic peptide (NT-proBNP) was measured in 618 incident haemodialysis patients, randomised to either high-flux or low-flux. Characteristics of patients with NT-proBNP levels below or above the median were descriptively analysed and survival analysis was performed. RESULTS: Median NT-proBNP value was 2,124 pg/ml, with 1,854 pg/ml in the high-flux and 2,919 pg/ml in the low-flux group. Survival probability was lowest in patients with both a history of cardiovascular disease and NT-proBNP values above the median (p < 0.001). A multivariate Cox proportional hazard model showed interaction between presence of cardiovascular diseases and NT-proBNP levels above the median. CONCLUSIONS: NT-proBNP is an independent predictor of mortality also in incident haemodialysis patients. Lower concentrations associated with high-flux dialysis suggest a possible biological link to improved survival in this group.