Search Results (36)

Background/Objectives: Protein-bound uremic toxins (PBUTs), particularly p-cresyl sulfate (PCS) and indoxyl sulfate (IS), are associated with cardiovascular toxicity and increased mortality. Conventional hemodialysis (HD) removes PBUTs poorly, and the efficacy of medium cut-off (MCO) dialyzer membranes remains uncertain. Furthermore, PBUT production is influenced by gut microbial metabolism and can be modified through diet. We hypothesized that MCO dialysis would provide superior clearance of PCS and IS compared with online hemodiafiltration (OL-HDF), and that combining MCO dialysis with increased dietary fiber and short-chain fatty acid (SCFA) intake would further reduce PBUT levels. Methods: In this prospective randomized trial, 62 maintenance HD patients underwent a 2-week wash-in period with high-flux HD (HF-HD) and were then randomized to MCO-HD (EXP) or OL-HDF (CON). After a 4-week intervention with the assigned dialysis modality, both groups continued with the same dialysis treatment and received an 8-week dietary intervention consisting of 19 g/day fiber and 1 g/day sodium propionate. The study concluded with a 4-week wash-out period on HF-HD. Primary outcomes were total serum PCS and IS levels measured at four timepoints. Results: Fifty-two patients completed the study. No significant changes in PCS or IS were observed after the dialysis-only intervention. PCS levels remained stable throughout the study. When the aligned dialysis regimen was combined with the dietary intervention, IS levels were significantly lower in the CON than in the EXP group (31.5 ± 10.3 vs. 42.0 ± 15.8 µmol/L; p = 0.006), with a partial rebound after wash-out in the CON group (39.6 ± 20.9 µmol/L; p = 0.003). Conclusions: While MCO-HD and OL-HDF had a similar effect on serum PCS and IS concentrations, only OL-HDF combined with the dietary intervention significantly reduced IS levels. Full article

Background: Online hemodiafiltration (HDF) represents the most advanced form of kidney replacement therapy, combining diffusive and convective transport to enhance the removal of uremic toxins across a wide molecular spectrum. Achieving high convective volumes is a key determinant of treatment efficacy and has been associated with improved survival. Beyond small solutes, HDF targets middle molecules and protein-bound uremic toxins (PBUTs), including β₂-microglobulin, inflammatory cytokines, and other large uremic compounds implicated in cardiovascular and systemic complications. Aims: This narrative review examines advances in dialysis membrane materials, dialyzer design, and monitoring technologies that optimize mass transfer in HDF. It focuses on the interplay between membrane permeability, hemocompatibility, and convective dose delivery, and discusses how these engineering developments translate into clinical performance. Key mechanisms: Recent progress in synthetic polymer membranes, particularly polysulfone- and polyethersulfone-based systems, and hollow-fiber manufacturing has enabled improved control of pore size distribution, hydraulic permeability, and sieving characteristics. These developments enhance the clearance of middle molecules and selected PBUTs while preserving essential proteins such as albumin. Mechanistic insights into internal filtration, protein polarization, and Donnan effects highlight the complex transport processes occurring within the dialyzer and their interaction with automated HDF systems. Expanded hemodialysis and high-volume HDF approaches further increase the removal of larger solutes but require careful management to limit albumin loss and maintain hemocompatibility. Clinical implications: Optimized membrane design, combined with advanced HDF machine algorithms, allows delivery of high convective volumes under safe and stable conditions, improving removal of β₂-microglobulin, cytokines, and other clinically relevant toxins associated with inflammation and cardiovascular risk. However, treatment must remain individualized, considering electrolyte balance, albumin preservation, and patient-specific factors such as inflammation and nutritional status. Mechanistic modeling supports understanding of transport phenomena but must be interpreted cautiously when translated into clinical practice. Conclusions: Advances in membrane science, dialyzer engineering, and monitoring technologies have strengthened the role of HDF as a precision-based renal replacement therapy. Continued innovation aimed at optimizing middle-molecule and PBUT clearance while preserving albumin and treatment stability is essential to improve patient outcomes and support the broader implementation of HDF as a mainstream dialysis modality. Full article

Protein-bound uremic toxins (PBUT), particularly indoxyl sulphate (IS) and p-cresyl sulphate (pCS), are poorly removed by conventional haemodialysis because of their strong albumin binding. These toxins are associated with cardiovascular morbidity and mortality in haemodialysis patients. Displacer molecules such as ibuprofen enhance PBUT clearance by competing for albumin-binding sites, but the optimal dose and route of administration remain unclear. The aim of this study was to evaluate the effect of different ibuprofen doses, infusion durations, and routes of administration on the removal of IS and pCS during on-line hemodiafiltration (OL-HDF). In this prospective, single-centre, crossover study, 21 chronic haemodialysis patients receiving intradialytic analgesia underwent nine OL-HDF sessions. Ibuprofen was administered at two doses (400 or 800 mg) either in the arterial pre-filter line (infusion over 1 h, 2 h, or 3 h) or in the venous post-filter line (30 min). Reduction ratios (RR) of total IS and pCS were determined by LC-MS and corrected for haemoconcentration. Statistical analysis included repeated-measures ANOVA with post-hoc testing. Baseline RR for IS and pCS were 53.7 ± 9.9% and 47.1 ± 10.9%, respectively. The highest RR was achieved with 800 mg ibuprofen infused via the arterial line over 2 h (IS: 60.8 ± 8.6%; pCS: 57.8 ± 9.7%). All arterial-line 800 mg regimens and the 3-h 400 mg infusion significantly improved pCS clearance versus baseline; IS clearance improved significantly only with arterial-line 800 mg regimens and with the 400 mg 3-h infusion. Infusion rate (1–3 h) had no significant effect on RR within the same dose group. Pain scores decreased significantly after dialysis regardless of ibuprofen regimen. Arterial-line administration of ibuprofen enhances total IS and pCS removal during OL-HDF, with higher doses yielding greater clearance. Prolonged low-dose infusion appears similarly effective for pCS and may reduce systemic exposure, potentially lowering toxicity risk. These findings support the arterial line as the preferred route for displacer administration in clinical practice. Full article

Background and Objectives: On-line hemodiafiltration (OL-HDF) has been proposed as an alternative to conventional hemodialysis (HD) for patients with end-stage chronic kidney disease (CKD). Randomized controlled trials suggest that OL-HDF may reduce mortality, particularly when the convection volume (CV) exceeds 23 L/1.73 m² per session. However, achieving this target depends on local practices and may be limited to selected populations. The CONVINCE trial reported a 97% success rate using a structured optimization protocol, but its applicability to unselected real-world populations remains uncertain. This study aimed to evaluate the incidence of high CV in OL-HDF among unselected patients managed under routine conditions with a standardized optimization protocol. Methods and Materials: This prospective cohort study (May–October 2024) included 67 unselected incident and prevalent patients undergoing HD or HDF in a hospital-based dialysis center. All patients were switched to post-dilution OL-HDF following the CONVINCE optimization protocol, which involved stepwise increases in blood flow, adjustment of filtration fraction, and optimization of session duration. Results: The mean age was 68.8 ± 14.9 years; 56.7% were male. Blood flow increased from 283 to 338 mL/min (p < 0.001), and the use of dialyzers > 2 m² increased from 36% to 68% (p < 0.003). Kt/V improved from 1.22 to 1.6 (p < 0.01). CV increased by ~2 L from M1 onward and was sustained through M6, correlating positively with blood flow, session duration, and Kt/V (all p < 0.01). Conclusions: Stepwise optimization protocol enabled sustained achievement of high CV (23.5 L/session) in 62.3% of patients, improving dialysis adequacy. Full article

Background and Objectives: Interdialytic blood pressure (BP) better reflects volume status and cardiovascular risk in hemodialysis (HD) patients than peridialytic readings. High-efficiency dialysis techniques—online hemodiafiltration (HDF) in pre-, post-, and mixed-dilution modes, and expanded hemodialysis (HDx) with medium cut-off membranes—aim to improve solute clearance and hemodynamic stability. Their comparative impact on interdialytic BP control remains unclear. This randomized cross-over study compared interdialytic BP profiles across these modalities under standardized treatment conditions. Materials and Methods: Sixteen clinically stable adults with end-stage kidney disease sequentially underwent high-flux HD, HDx, and HDF in pre-, post-, and mixed-dilution configurations, each for one month. Dialysis prescriptions, dry weight, and antihypertensive therapy remained constant. Home BP was measured twice daily on non-dialysis days, yielding ~3600 observations. Systolic (SBP), diastolic (DBP), and mean arterial pressure (MAP) were analyzed by repeated-measures ANOVA with Bonferroni correction. Results: Significant differences were found among modalities for SBP (p = 0.009), DBP (p = 0.004), and MAP (p < 0.001). HDx achieved the lowest mean BP values—SBP 129 (95% CI 127–131) mmHg; DBP 74 (95% CI 73–75) mmHg; MAP 93 (95% CI 91–94) mmHg—significantly lower than high-flux HD and post-dilution HDF (p < 0.05). Differences versus pre- and mixed-HDF did not reach significance. Conclusions: HDx provided modest but consistent reductions in interdialytic BP compared with diffusive and convective high-efficiency modalities. Trial Registration: Ethics Committee of the Medical University of Gdańsk (NKBBN/479-759/2022). Full article

The number of patients with end-stage renal disease continues to grow worldwide, placing increasing demands on dialysis technologies. Conventional hemodialysis remains the dominant modality but is often limited by frequent intradialytic hypotension and the insufficient removal of medium-sized toxins. Intermittent infusion hemodiafiltration (I-HDF) is an emerging, hybrid dialysis technique that combines standard hemodialysis with the cyclic backfiltration of ultrapure dialysate. This approach enables dynamic blood volume control and periodic backflushing of the dialyzer membrane. Recent clinical studies demonstrate that I-HDF can reduce intradialytic hypotension incidence, improve systemic and microcirculatory perfusion, and enhance the clearance of middle molecules such as β₂-microglobulin, while minimizing albumin loss. These benefits are particularly relevant to toxin clearance and hemodynamic stabilization, key priorities in optimizing dialysis outcomes. Large-scale cohort data suggest that I-HDF may be linked to improved long-term survival in dialysis patients. Given its physiological advantages and operational flexibility, I-HDF may also offer a practical solution in healthcare systems with limited access to high-volume online hemodiafiltration or kidney transplantation. Further research is warranted to develop individualized infusion protocols and validate its broader applicability. Full article

The management of end-stage kidney disease (ESKD) poses a substantial clinical and economic challenge, characterized by a growing patient burden, rising healthcare costs, and persistent unmet needs to enhance survival outcomes and quality of life. Background/Objectives: Conventional high-flux hemodialysis (HD) remains the dominant form of renal replacement therapy for ESKD but is still associated with substantial morbidity and mortality. High-volume post-dilution online hemodiafiltration (HVHDF) offers a promising alternative by enhancing the convective removal of uremic toxins. Methods: We conducted a narrative review of randomized controlled trials, meta-analyses, real-world cohort studies, and registry analyses published between 2010 and 2024. Evidence was categorized into short-term, medium-term, and long-term outcomes, including hemodynamic stability, inflammation, anemia, infection risk, cardiovascular events, cognitive decline, quality of life, and survival. Results: HVHDF improves short-term outcomes by enhancing toxin clearance, stabilizing blood pressure, reducing inflammation and oxidative stress, and improving anemia management. Medium-term benefits include improved nutritional status, reduced hospitalizations related to infections, and improved neurological and immune function. Long-term data from major trials (e.g., ESHOL, CONVINCE) and large real-world studies show consistent reductions in all-cause and cardiovascular mortality, particularly with convection volumes ≥ 23 L/session. A clear dose–response relationship supports the clinical relevance of convection volume targets. HVHDF has also shown benefits in preserving cognitive function and enhancing health-related quality of life. Conclusions: Strong and converging evidence supports HVHDF as a superior dialysis modality. Given its survival benefits, better tolerance, and broader impact on patient outcomes, HVHDF should be considered the new standard of care in dialysis, especially in light of the recent regulatory approval of the machine that provides the ability to perform HDF in the United States. Full article

This review highlights recent insights into the pathophysiology and therapeutic strategies for improving biocompatibility in hemodialysis. Hemodialysis activates the innate immune system, particularly the complement cascade and neutrophils, leading to acute microinflammation. Interleukin-8 (IL-8), which increases during dialysis, promotes neutrophil chemotaxis and neutrophil extracellular trap (NET) formation, triggering myeloperoxidase (MPO) release and oxidative stress. Neutrophil accumulation in atherosclerotic plaques exacerbates vascular inflammation through IL-6 upregulation. Elevated levels of IL-8, MPO, and NET-related biomarkers are associated with increased all-cause and cardiovascular mortality in dialysis patients. Strategies to mitigate these effects include the use of advanced membrane materials (e.g., AN69, vitamin E-coated, polymethyl methacrylate), novel dialysis modalities (e.g., high-volume online hemodiafiltration, cool dialysate, hydrogen-enriched dialysate), and citrate-based anticoagulation. These approaches aim to suppress complement activation, reduce oxidative stress, and limit neutrophil-induced damage. Enhancing biocompatibility is crucial for reducing cardiovascular complications and improving outcomes in dialysis patients. Suppressing the innate immune response during dialysis may become a future cornerstone in extracorporeal blood purification therapy. Full article

Patients on standard hemodialysis (HD) show insufficient clearance of medium-molecular-weight uremic toxins, resulting in long-term complications. In this study we investigated the effectiveness of expanded HD (xHD) in the clearance of medium-molecular-weight uremic substances. This prospective study included patients on standard thrice-weekly HD. Participants were treated with xHD for 4 weeks, and the clearance of urea and β2-microglobulin was measured at the beginning and at the end of the study and compared with standard HD (sHD). Moreover, we investigated the clearance of Su-PAR, MCP-1, and activin, comparing sHD, xHD, and online hemodiafiltration (HDF). xHD had the same efficiency in the removal of low-molecular-weight substances compared to sHD but led to a significant decrease in β2-microglobulin levels from the first application of the method (sHD: from 36.9 ± 10.6 to 39.7 ± 18.9 mg/dL, p = 0.595 vs. 1st xHD: from 40 (36.5, 41.8) to 11 (9.8, 13.2) mg/dL, p = 0.008 vs. after 4 weeks on xHD: from 31.5 (28.5, 34.5) to 8.7 (8.2, 9.0) mg/dL, p = 0.008). Moreover, pre-session β2-microglobulin levels significantly decreased after 4 weeks on xHD. Su-PAR, MCP-1, and activin during xHD were also significantly reduced. xHD leads to a significant and cumulative reduction in medium-molecular-weight uremic toxins compared to standard HD. Full article

Background/Objectives: High-flux online hemodiafiltration (OL-HDF) appears to be associated with better survival than hemodialysis (HD). In Brazil, OL-HDF is only affordable for patients with private health insurance. Although observational studies have shown a survival advantage with OL-HDF, even in Brazil, it is unclear whether this benefit applies to patients without private health insurance. We compared overall and cardiovascular mortality between OL-HDF and HD in patients treated exclusively through the public health care system. We hypothesized that patients on OL-HDF would have a higher survival rate than those on HD. Methods: This is an observational cohort study. Adult patients on maintenance hemodialysis or OL-HDF for at least one month during the period between 1 September 2022 and 1 December 2024 were enrolled into the study. The primary outcome was all-cause mortality. The secondary outcome was cardiovascular mortality. Fine-Gray sub-distribution hazard models were used to evaluate survival in the presence of competing events (kidney transplant and recovery of renal function). Results: Patients on HD (N = 321) and OL-HDF (N = 48) were similar in age, race, sex, and vascular access. Patients on HD were more likely to have diabetes (54.0% vs. 29.2%, p = 0.001) and spent more hours per week on dialysis (11.2 ± 1.8 vs. 10.5 ± 1.6 h, p = 0.006). In an adjusted Fine-Gray model, the hazard of death for patients on OL-HDF was 68% lower than that for patients on HD, and the risk of death for patients with an arteriovenous fistula was 55% lower compared to those with a catheter. Cardiovascular mortality did not differ between the groups. Conclusions: These findings suggest that OL-HDF is associated with an overall higher survival rate compared to HD, even for patients without private health insurance. Full article

As chronic kidney disease (CKD) prevalence rises, optimizing hemodialysis remains essential. While online hemodiafiltration (OL-HDF) is the gold standard, expanded hemodialysis (HDx), i.e., using high-performance dialyzers in standard hemodialysis, remains the most common clinical practice. Medium cutoff (MCO) membranes aim to enhance middle-molecule removal while preserving protein selectivity, although most studies evaluate them in OL-HDF. To this end, this study aims to compare the Xevonta-Hi (B. Braun), a high-flux (HF) polysulfone dialyzer, and the ELISIO-HX (Nipro), an MCO polyethersulfone dialyzer, in standard hemodialysis. In a prospective, observational study, seven stable patients sequentially received treatment with each dialyzer over four weeks. Pre- and post-dialysis levels of small and middle uremic molecules and inflammatory markers—including procalcitonin, prolactin, serum amyloid A, placental growth factor, interleukin-6, haptoglobin, ceruloplasmin, transferrin, prealbumin, and C-reactive protein—were measured. Both dialyzers demonstrated excellent clearance of small and middle molecules, with no significant differences in efficacy. Albumin and total protein losses remained minimal. Moderate reductions in serum amyloid A, placental growth factor, and interleukin-6 were observed, while no significant reductions occurred in the remaining inflammatory markers. These findings support the safety and effectiveness of both MCO and HF dialyzers in standard hemodialysis. Full article

Poor water treatments and concentrates to prepare dialysis fluids favor bacterial growth-producing pyrogens (e.g., endotoxins) that may cross hemodialysis, particularly high-flux, membranes. This puts hemodialysis patients at risk of acute bacteremia, pyrogenic reactions, long-term complications, loss of residual renal function, and poor nutritional status. Consequently, regulatory bodies worldwide recommend using ultrapure dialysis fluid for routine hemodialysis. Requests are also growing for the online production of sterile non-pyrogenic substitution fluid from ultrapure dialysis fluid. This way, large volumes of infusion solution may be safely and economically produced, enabling more end-stage kidney disease patients to benefit from the greater capacity of hemodiafiltration to remove toxins than purely diffusive hemodialysis treatment. Ultrapure dialysis and substitution fluids are often produced upstream from hemodialyzers by online filtration of standard dialysis fluid through cascades of bacteria- and endotoxin-retentive filters (ETRFs). Commercial ETRFs differ for membranes, operation, performance, duration and maintenance protocols, connection to a dialysis machine, disinfection procedures, and replacement schedule. Although suboptimal ETRF choice may increase treatment costs, the difficulty in gathering comparative information on commercial ETRFs complicates their selection. To aid dialysis centers in selecting the most convenient and suitable ETRF for their needs, herein, relevant characteristics of commercial ETRFs are reported and critically reviewed for a quick yet effective comparison. Full article

Introduction: The potassium removed by various dialysis methods (pre- and post-dilution on-line hemodiafiltration) is not clear in the literature. The aim of the study was to investigate the amount of potassium eliminated with each session of pre- or post-dilution on-line hemodiafiltration with collection of the total ultrafiltrate in a tank. Materials and Methods: We studied in 10 dialyzed patients the removal of potassium by a polyetherosulfone dialysis filter. We sought to investigate whether the amount removed is related to filter surface area and type of dialysis. We examined the removal of potassium by on-line hemodiafiltration and post-dilution with high-flux filters, surface areas 2.5 m² (Group A) and 2.1 m² (Group B). We repeated the same process with low-flux filters with conventional hemodialysis (Group C), as well as with pre-dilution on-line hemodiafiltration and 2.5 m² surface area filters (Group D). Results: Significantly higher potassium removal was noted with post-dilution on-line hemodiafiltration versus conventional haemodialysis, which was not affected by filter surface area, and also higher with pre-dilution on-line hemodiafiltration versus all other methods. The amounts of removed potassium even exceeded 300 mmol of potassium/dialysis session in some cases. Conclusions: It is concluded that, with on-line hemodiafiltration, much higher amounts of potassium are removed (mainly with pre-dilution) compared to conventional haemodialysis. The amount removed is not affected by the surface of the filter. The lower potassium levels of dialysate play an important role in this elimination. Full article

Background: High-volume online hemodiafiltration (OL-HDF) has proven to be the most efficient dialysis modality and to offer better clinical outcomes in patients on hemodialysis. Longer and more frequent dialysis sessions have demonstrated clinical and survival benefits. Methods: A single-center observational study of the first one hundred patients on nocturnal every-other-day OL-HDF was conducted with the aim of reporting the experience with this treatment schedule and evaluating analytical and clinical outcomes as well as the patient and technique survival. Results: Nocturnal OL-HDF on alternate days was highly accepted, with no adverse symptoms, good clinical tolerance, and maintained active work in 62%. Kt, and the convective volume increased from 67.6 ± 12 L to 105.4 ± 11.7 L, and from 27.1 ± 4.6 L to 48.1 ± 6.4 L, respectively, from the baseline to 24 months. An improved calcium–phosphate balance and blood pressure control were observed, as the use of phosphate binders and antihypertensive medications decreased from 76.7% to 3.3% and from 56.7% to 28.3%, respectively. Furthermore, 58.3% of patients required phosphate supplementation in the dialysis fluid to prevent intradialytic hypophosphatemia. Additionally, doses of iron and erythropoiesis-stimulating agents were reduced. The global patient survival was 94% at the end of the follow-up. It was higher in those on the transplant waiting list, with 98.1% survival compared to 84.6% in non-wait-listed patients at 24 months. The main reason for treatment discontinuation was kidney transplantation, accounting for 78.4% of the 88 withdrawals, while death was the leading cause of discontinuation in non-listed patients (41.6%). Conclusions: Nocturnal every-other-day OL-HDF is a well-tolerated dialysis regimen that offers significant clinical benefits, which may positively impact morbidity and mortality. Additionally, it allows patients to integrate the treatment into their social and occupational lives. Full article

Background/Objectives: The cost resulting from peritoneal dialysis (PD), conventional hemodialysis (HD) and online hemodiafiltration (OL-HDF) in pediatric patients with end-stage renal disease (ESRD) has not been estimated to date in Greece. The present single-center retrospective study aimed to estimate the mean annual cost of the above methods, as well as the individual components of this cost. Methods: Twenty pediatric patients undergoing the three different methods of renal replacement therapy were included in this study. Their mean total annual cost was estimated by the method of micro-costing and the bottom-up approach. Results: The mean total annual cost for PD patients (n = 7) was estimated at EUR 56,676.04; for conventional HD patients (n = 9), it was EUR 39,786.86; and for OL-HDF patients (n = 4), it was EUR 43,894.73. The PD method was found to be more expensive than the other two methods (p < 0.001 vs. conventional HD and p = 0.024 vs. OL-HDF). PD consumables used for daily application had the greatest contribution to the total annual cost. The total mean annual cost in the groups of patients undergoing HD and OL-HDF did not differ significantly (p = 0.175). The total operating cost of the renal dialysis unit had the greatest contribution to the total mean annual costs of both the conventional HD and OL-HDF techniques. Conclusions: This cost analysis provides useful information to healthcare policymakers who make decisions about the treatment of children with ESRD. Full article