A Review of Commercial Developments and Recent Laboratory Research of Dialyzers and Membranes for Hemodialysis Application

Dialyzers have been commercially used for hemodialysis application since the 1950s, but progress in improving their efficiencies has never stopped over the decades. This article aims to provide an up-to-date review on the commercial developments and recent laboratory research of dialyzers for hemodialysis application and to discuss the technical aspects of dialyzer development, including hollow fiber membrane materials, dialyzer design, sterilization processes and flow simulation. The technical challenges of dialyzers are also highlighted in this review, which discusses the research areas that need to be prioritized to further improve the properties of dialyzers, such as flux, biocompatibility, flow distribution and urea clearance rate. We hope this review article can provide insights to researchers in developing/designing an ideal dialyzer that can bring the best hemodialysis treatment outcomes to kidney disease patients.

Effects of Roxadustat on the Anemia and Iron Metabolism of Patients Undergoing Peritoneal Dialysis

Background: We investigated the effects of roxadustat on the anemia, iron metabolism, peritoneal membrane function, and residual renal function; and determined the factors associated with the administration of roxadustat in patients who were undergoing peritoneal dialysis.Methods: We retrospectively analyzed the changes in hemoglobin, serum ferritin, transferrin saturation (TSAT), 4-h dialysate/plasma creatinine, and renal weekly urea clearance over the 24 weeks following the change from an erythropoiesis-stimulating agent (ESA) to roxadustat in 16 patients who were undergoing peritoneal dialysis and had anemia (Roxadustat group). Twenty-three peritoneal dialysis patients who had anemia and continued ESA served as a control group (ESA group).Results: There were no significant differences in hemoglobin, serum ferritin, TSAT, 4-h dialysate/plasma creatinine, or renal weekly urea clearance between the two groups at baseline. The hemoglobin concentration was significantly higher in the Roxadustat group than in the ESA group after 24 weeks (11.6 ± 1.0 g/dL vs. 10.3 ± 1.1 g/dL, p < 0.05), whereas the ferritin concentration and TSAT were significantly lower (139.5 ± 102.0 ng/mL vs. 209.2 ± 113.1 ng/mL, p < 0.05; and 28.1 ± 11.5% vs. 44.8 ± 10.4%, p < 0.05, respectively). The changes in 4-h dialysate/plasma creatinine and renal weekly urea clearance did not differ between the two groups. Linear regression analysis revealed that the serum potassium concentration correlated with the dose of roxadustat at 24 weeks (standard coefficient = 0.580, p = 0.019).Conclusion: Roxadustat may improve the anemia and reduce the serum ferritin and TSAT of the peritoneal dialysis patients after they were switched from an ESA, without association with peritoneal membrane function or residual renal function.

Improving Clearance for Renal Replacement Therapy

The adequacy of hemodialysis is now assessed by measuring the removal of the single solute urea. The urea clearance provided by current dialysis methods is a large fraction of the blood flow through the dialyzer, and therefore cannot be increased much further. Other solutes which are less effectively cleared than urea may however contribute more to the residual uremic illness suffered by hemodialysis patients. We here review a variety of methods which could be employed to increase the clearance of such non-urea solutes. New clinical studies will be required to test the extent to which increasing solute clearances improves patients' health.

Changes in extracellular water with hemodialysis and fall in systolic blood pressure

Introduction: Intra-dialytic hypotension (IDH) remains the most common complication with outpatient hemodialysis (HD) sessions. As fluid is removed during HD, there is contraction of the extracellular volume (ECW). We wished to determine whether the fall in ECW was associated with a fall in systolic blood pressure (SBP). Methods: We retrospectively reviewed the records of adult dialysis outpatients attending for their midweek sessions who had corresponding pre- and post-HD bioimpedance measurements of ECW. Result: We reviewed 736 patients, median age 67 (54–76) years, 62.8% male, 45.7% diabetic with a median dialysis vintage of 24.4 (9.2–56.8) months. The percentage fall in ECW (ECW%) was associated with post-dialysis systolic blood pressure (SBP) ( r = −0.14, p < 0.001). Patients with SBP falls of >20 mmHg had a greater fall in ECW% compared to patients with stable SBP 7.6 (4.6–10.1) vs 6.0 (4.0–8.5), p < 0.001). Patients with greater dialyzer urea clearance had greater fall in ECW% ( r = 0.19, p < 0.001). In a logistic model an increased fall in ECW% was associated with weight loss (odds ratio (OR) 1.88, 95% confidence limits (CL) 1.62–2.176, p < 0.001), and session duration (OR 1.45 (CL 1.05–1.99), p = 0.024), and negatively with hemodiafiltration compared to hemodialysis (OR 0.37 (0.19–0.74) p = 0.005 and dialysate sodium to plasma gradient (OR 0.95 (CL 0.90–0.99), p = 0.021). Conclusion: We observed an association between the reduction in ECW and SBP with dialysis. Our results would advocate monitoring ECW changes during dialysis and developing biofeedback devices to control ultrafiltration and dialysate sodium to reduce the risk of IDH.

P1248DOES INCREMENTAL HAEMODIALYSIS PRESERVE NATIVE KIDNEY FUNCTION? A MULTI-CENTRE FEASIBILITY RANDOMISED CONTROL TRIAL

Background and Aims Incremental HD is a method of individualising haemodialysis (HD) dose according to level of residual renal function(RRF) such that as RRF reduces, HD dose is upwardly adjusted. Retrospective data suggest potential benefit of this approach in preserving RRF, a key predictor of survival for dialysis patients. Method A randomised, intention-to-treat, multi-centre trial was designed to determine the feasibility of a future definitive trial of incremental HD to establish if this approach preserves RRF. The trial was designed to estimate effect size of potential benefit in terms of RRF. 55 patients with RRF urea clearance≥3ml/min/1.73m2 BSA and within 3 months of starting HD were randomised across 4 UK dialysis centres to either conventional 3x weekly HD for 3.5-4 hours or incremental HD. The incremental HD protocol involved initiation of HD 2x weekly after randomization and upward adjustment of HD frequency and time as RRF was lost. In the conventional HD arm, patients were dialysed to ensure Standard Kt/VDialysis&gt;2.0. In the incremental HD arm, patients were dialysed to ensure Standard Kt/VDialysis+Standard Kt/VResidual Renal Function&gt;2.0 so both groups were dialysed to the same urea clearance target, except that urea clearance incorporated RRF in the incremental HD arm. Follow up was for 6 months (primary outcome data) but secondary outcome data will be for 12m. Patients were withdrawn for transplant, dialysis modality change or for patient choice. The primary outcome was rate of change of RRF in the first 6 months after randomization (effect size of intervention). Recruitability, retainability, protocol adherence and rate of adverse events were also measured as a primary objective. As a secondary outcome, we determined proportion of patients with urea clearance≥2 and ≥3ml/min /1.73m2 BSA at the 6 month time point. Impact of dialysis treatment was measured using questionnaire-based assessments at baseline and 6 months. Results 26 patients were randomised to standard HD and 29 to incremental HD. Baseline demographics including age, weight, haemoglobin, blood pressure, Charleson Comorbidity Index, were not significantly different between study arms. Baseline residual renal urea clearance was 5.1 ± SD 1.8 ml/min/1.73m2 BSA in the standard HD arm and 5.72 ± SD 2.49 in the incremental HD arm. 6 months, residual renal urea clearance reduced to 2.68±SD 1.73 in the standard HD arm and 3.80±SD 1.85 in the incremental arm. In the first 6 months, 3 patients recovered to dialysis independence (standard arm=1, incremental arm=2). Slope of RRF was not significantly different between two arms (p=0.39). The proportion of patients with significant urea clearance&gt;2ml/min/1.73m2 BSA at 6 months was significantly higher in the incremental HD arm (92%) compared to the standard HD arm (65%), p=0.032. Rate of major adverse cardiac events, fluid overload, hyperkalaemia, vascular access events, deaths and infections did not differ significantly between groups. There were 2 deaths in the standard HD arm (in 4025 patient days) versus 1 in the incremental HD arm in the first 6 months(4666 patient days). There was no significant difference in Clinical Frailty Score, Montreal Cognitive Assessment score, depression score (PHQ-9), Quality of Life (EQ-5D-5L) and Illness Intrusiveness Rating Scale between groups at baseline and 6m time points. Conclusion Rate of loss of RRF (slope) was not significantly different between incremental HD and standard HD arms but incremental HD was associated with significantly higher probability of retaining urea clearance&gt;2ml/min/1.73m2. There was no evidence of any clinical detrimental effect of incremental HD in terms of mortality, fluid overload or hyperkalaemic events. Incremental HD does not appear to be harmful and may confer a small benefit to preservation of residual renal function. A definitive study is required to define clinical benefits further.