Dosing of Aminoglycosides in Chronic Kidney Disease and End-Stage Renal Disease Patients Treated with Intermittent Hemodialysis.

BACKGROUND: The dosing of aminoglycosides (AGs) in patients with kidney disease is challenging due to their markedly prolonged half-life, which renders pulse dosing schedules unsuitable. We performed a review of the literature that describes the pharmacokinetics of, and dosing recommendations for, AG for patients with abnormal renal functions and various renal replacement therapy modalities, focusing on patients treated with intermittent hemodialysis (iHD). SUMMARY: During one iHD session, dialysis removes a remarkable amount of the drug regardless of the dialyzer type. In patients with severely reduced kidney functions, the distribution phase is prolonged, which needs to be taken into account when drawing samples shortly after drug administration or following an iHD session. KEY MESSAGES: The doses recommended for the pulse dosing of patients without kidney disease leads to unacceptably high overall systemic exposure for patients with severely reduced kidney functions even with dosing intervals extended up to 48 h. Therefore, lower doses accompanied by extended dosing intervals must be applied for this patient group. The clinical evidence and current recommendations support the dosing of AG following, rather than before, HD sessions. In patients with end-stage kidney disease, the samples for TDM of AGs should not be drawn earlier than 2 h after end of the infusion and 4 h after the end of iHD session to allow full (re)distribution of the drug.

Medium Cut-Off Dialysis Membranes: Can They Have Impact on Outcome of COVID-19 Hemodialysis Patients?

INTRODUCTION: Severe acute respiratory syndrome coronavirus-2 may lead to high levels of expression of inflammatory cytokines. Medium cut-off (MCO) membranes may make greater clearances for large-middle molecules (including cytokines) than low-flux (LF) membranes. In this study, we aimed to evaluate the impact of MCO membranes on outcome of COVID-19 patients on hemodialysis (HD). METHODS: Sixty COVID-19 HD patients were included in this study. The patients were categorized into 2 groups regarding type of HD membranes. Clinical data were taken from medical records. RESULTS: Initial crp and ferritin levels, which are surragates of cytokine storm and severity of disease in COVID-19, were significantly higher in MCO membrane group compared to LF group (p = 0.037 and 0.000, respectively). Although there were more patients with severe disease in MCO group, there were no significant differences regarding need for intensive care unit and death. CONCLUSION: It may be an option to use MCO membranes in HD patients with COVID-19 in order to reduce cytokine levels and prevent cytokine storm.

The use of different dialysis membranes in therapy of patients with multiple myeloma.

Free light chains accumulation is the reason of kidney injury in patients with multiple myeloma. The removal of free light chains can improve patients prognosis and survival, and in some cases allows for dialysotherapy discontinuation. Unfortunately, conventional dialysis is not effective enough in terms of free light chains removal. New high cut-off (HCO) techniques remove free light chains more effectively than conventional dialysis. In some cases, this technique may turn out better than hemodiafiltration. However, there are some differences between specific techniques in the removal of kappa and lambda light chains. Lambda light chains are better removed by polymethyl methacrylate membranes with a change of filter during dialysis. Kappa light chains are thoroughly removed by polymethyl methacrylate membranes and HCO (35,000 Da) polysulfone membranes. Unfortunately, it is very difficult to differentiate between the effect of HCO dialysis therapy and concomitant chemotherapy because some of the data is not fully conclusive. Using the proper technique for an individual patient may give optimally effective treatment results.

ß-trace protein is highly removed during haemodialysis with high-flux and super high-flux membranes.

BACKGROUND: Serum ß-trace protein (ßTP, MW 23-29 kDa) is a marker of GFR impairment in renal patients. Recent papers propose to predict residual renal function (RRF) in maintenance haemodialysis (MHD) patients from serum concentrations of ßTP and other small proteins, avoiding the collection of urine. Few data are available on the removal of ßTP in patients treated with dialysis membranes with different flux characteristics. The aim of this study was to evaluate the effects of haemodialysis with low-flux, high-flux and super high-flux membranes on serum concentrations of ßTP in MHD patients with null RRF. METHODS: Serum ßTP concentrations were measured before and after the first dialysis of the week in 51 MDH patients treated by low-flux (n = 24), high-flux (n = 17), or super high-flux (n = 10) membranes. The removal of ß2-microglobulin (ß2M, MW 11.8), cystatin C (Cys, MW 13.3), urea and creatinine was also analyzed. RESULTS: Low-flux membranes did not remove ßTP, ß2M and Cys whose concentration increased at the end of dialysis. High-flux membrane removed more efficiently ß2M and Cys than ßTP. Super high-flux membrane had the highest efficiency to remove ßTP: mean reduction ratio (RR) 53.4%, similar to ß2M (59.5%), and Cys (62.0%). CONCLUSIONS: In conclusion, the plasma clearance of small proteins and particularly of ßTP is dependent from the permeability of the dialysis membranes Therefore, the reliability of the formulas proposed to predict RRF from serum ßTP and other LMWP may be affected by the different permeability of the dialysis membranes.

The effect of two different high-flux dialysis membranes on insulin resistance in non-diabetic end-stage renal disease patients.

OBJECTIVE: The aim of this study was to investigate the effect of two different types of high-flux dialysis membranes on insulin resistance among patients who are receiving hemodialysis (HD) due to end-stage renal failure (ESRF). MATERIALS AND METHODS: Forty-six (21 female, 25 male) patients were included in the study, who were on HD treatment due to stage-5 chronic renal failure. Prior to the study, fasting insulin resistance via Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) and fractioned urea clearance (Kt/V) values were calculated using the urokinetic model. The polysulfone (PS) dialysis membrane of all patients included in the study was replaced with "polyarylethersulfone, polyvinylpyrrolidone, polyamide (PPP)" high-flux membrane that has the same surface area over 12 weeks. At the end of the 12-week period, HOMA and Kt/V values were recalculated. RESULTS: At the end of the 12-week period, Kt/V values rose statistically significant from 1.575 to 1.752 (p = 0.002). HOMA-IR values declined, though not statistically significant, from 3.268 to 2.926 (p = 0.085). PPP high-flux membrane increased the Kt/V values significantly compared to the PS membrane, while it decreased the insulin resistance and increased insulin sensitivity. CONCLUSION: The two different types of high-flux dialysis membranes used for HD have different effects on insulin sensitivity. Compared to the PS membrane, PPP high-flux membrane decreased insulin resistance by increasing insulin sensitivity among non-diabetic ESRF patients.

Dialysis nanocomposite membranes based on carbon nanoforms inhibiting blood plasma protein adsorption.

BACKGROUND: Protein adsorption on medical devices in contact with blood is a significant issue during renal replacement therapy. Main forces determining fouling are the electrostatic interactions between membrane and charged protein, but the dialysis membrane surface charges can be adjusted by modifying the polymer matrix to decrease the blood plasma protein adsorption. METHODS: In this study, polysulfone membranes (PSU) were modified by incorporation of carbon nanoparticles such as: multiwall carbon nanotubes (2 wt.% MWCNT), graphene oxide (1 wt.% GO), and graphite (5 wt.% GR) during manufacturing process (nonsolvent-induced phase separation, NIPS). The PSU flat sheet membrane was the reference sample. RESULTS: Observed morphology of nanocomposite membranes was similar (SEM imaging); all of them had finger-like pore structure with unimodal distribution of pore size and similar skin-to-support ratio (1:3). The carbon nanoadditives also influenced the surface wettability: hydrophobicity and surface free energy of membranes increased (polar components of energy were reduced, while the dispersive components were increased). CONCLUSION: The surface charge of nanocomposite membranes increased, when the polymer matrix has been modified with CNT or GR. This significantly affects the adsorption of proteins such as chicken (CSA) and bovine serum albumin (BSA) and reduces blood clotting on the membrane.

Medium Cutoff Versus High-Flux Hemodialysis Membranes and Clinical Outcomes: A Cohort Study Using Inverse Probability Treatment Weighting.

Rationale & Objective: This study investigated the effects on patients' outcomes of using medium cutoff (MCO) versus high-flux (HF) dialysis membranes. Study Design: A retrospective, observational, multicenter, cohort study. Setting & Participants: Patients aged greater than 18 years receiving hemodialysis at the Baxter Renal Care Services dialysis network in Colombia. The inception of the cohort occurred from September 1, 2017, to November 30, 2017, with follow-up to November 30, 2019. Exposure: The patients were divided into 2 cohorts according to the dialyzer used at the inception: (1) MCO membrane or (2) HF membrane. Outcomes: Primary outcomes were the hospitalization rate from any cause and hospitalization days per patient-year. Secondary outcomes were acute cardiovascular events and mortality rates from any cause and secondary to cardiovascular causes. Laboratory parameters were assessed throughout the 2-year follow-up period. Analytical Approach: Descriptive statistics were used to report population characteristics. Inverse probability of treatment weighting was applied to each group before analysis. All categorical variables were compared using Pearson's χ2 test, and continuous variables were analyzed with the t test. Baseline differences between groups with a value of >10% were considered clinically meaningful. Laboratory variables were measured at 5 consecutive time points. A between-patient effect was analyzed using a split-plot factorial analysis of variance. Results: The analysis included 1,098 patients, of whom 564 (51.3%) were dialyzed with MCO membranes and 534 (48.7%) with HF membranes. Patients receiving hemodialysis with MCO membranes had a lower all-cause hospitalization incidence rate (IR) per patient-year (IR = 0.93; 95% CI, 0.82-1.03) than those receiving hemodialysis with HF membranes (IR = 1.13; 95% CI, 0.96-1.30), corresponding to a significant incident rate ratio (MCO/HF) of 0.82 (95% CI, 0.68-0.99; P = 0.04). The frequency of nonfatal cardiovascular events showed statistical significance, with a lower incidence in the MCO group (incident rate ratio = 0.66; 95% CI, 0.46-0.96; P = 0.03). No statistically significant differences in all-cause time until death were observed (P = 0.48). Albumin levels were similar between the 2 dialyzer cohorts. Limitations: Despite the robust statistical analysis, there remains the possibility that unmeasured variables may still generate residual imbalance and, therefore, skew the results. Conclusions: The incidences of hospitalization and cardiovascular events in patients receiving hemodialysis were lower when dialyzed with MCO membranes than HF membranes. A randomized controlled trial would be desirable to confirm these results. Trial Registration: Clinical Trials.gov, ISRCTN12403265.

Influence of Dialysis Membranes on Clinical Outcomes: From History to Innovation.

Dialysis membranes were traditionally classified according to their material compositions (i.e., as cellulosic or synthetic) and on the basis of the new concept of the sieving coefficient (determined by the molecular weight retention onset and molecular weight cut-off). The advantages of synthetic polymer membranes over cellulose membranes are also described on the basis of their physical, chemical, and structural properties. Innovations of dialysis membrane in recent years include the development of medium cutoff membranes; graphene oxide membranes; mixed-matrix membranes; bioartificial kidneys; and membranes modified with vitamin E, lipoic acid, and neutrophil elastase inhibitors. The current state of research on these membranes, their effects on clinical outcomes, the advantages and disadvantages of their use, and their potential for clinical use are outlined and described.

Polyvinylpyrrolidone in hemodialysis membranes: Impact on platelet loss during hemodialysis.

INTRODUCTION: Hydrophilic modification with polyvinylpyrrolidone (PVP) increases the biocompatibility profile of synthetic dialysis membranes. However, PVP may be eluted into the patient's blood, which has been discussed as a possible cause for adverse reactions rarely occurring with synthetic membranes. We investigated the content of PVP and its elution from the blood-side surface from commercially available dialyzers, including the novel FX CorAL, with PVP-enriched and α-tocopherol-stabilized membrane, and link the results to the level of platelet loss during dialysis as a maker of biocompatibility. METHODS: Six synthetic, PVP containing, dialyzers (FX CorAL, FX CorDiax [Fresenius Medical Care]; Polyflux, THERANOVA [Baxter]; ELISIO [Nipro]; xevonta [B. Braun]) were investigated in the present study. The content of PVP on blood-side surface was determined with X-ray photoelectron spectroscopy (XPS). The amount of elutable PVP was measured photometrically after 5 h recirculation. The level of platelet loss was evaluated in an ex vivo recirculation model with human blood. FINDINGS: Highest PVP content on the blood-side surface was found for the polysulfone-based FX CorAL (26.3%), while the polyethersulfone-based THERANOVA (15.6%) had the lowest PVP content. Elution of PVP was highest for the autoclave steam-sterilized THERANOVA (9.1 mg/1.6 m2 dialyzer) and Polyflux (9.0 mg/1.6 m2 dialyzer), while the lowest PVP elution was found for the INLINE steam sterilized FX CorAL and FX CorDiax (<0.5 mg/1.6 m2 dialyzer, for both). Highest platelet loss was found for xevonta (+164.4% compared to the reference) and the lowest for the FX CorAL (-225.2%) among the polysulfone-based dialyzers; among the polyethersulfone-based dialyzers, THERANOVA (+95.5%) had the highest and ELISIO (-52.1%) the lowest platelet loss. DISCUSSION: Polyvinylpyrrolidone content and elution differ between commercially available dialyzers and were found to be linked to the membrane material and sterilization method. The amount of non-eluted PVP on the blood-side surface may be an important determinant for the biocompatibility of dialyzers.

Survival with low- and high-flux dialysis.

BACKGROUND: Besides advances in haemodialysis (HD), mortality rates are still high. The effect of the different types of HD membranes on survival is still a controversial issue. The aim of this COSMOS (Current management Of Secondary hyperparathyroidism: a Multicentre Observational Study) analysis was to survey, in HD patients, the relationship between the use of conventional low- or high-flux membranes and all-cause and cardiovascular mortality. METHODS: COSMOS is a multicentre, open-cohort, 3-year prospective study, designed to evaluate mineral and bone disorders in the European HD population. The present analysis included 5138 HD patients from 20 European countries, 3502 randomly selected at baseline (68.2%), plus 1636 new patients with <1 year on HD (31.8%) recruited to replace patients who died, were transplanted, switched to peritoneal dialysis or lost to follow-up by other reasons. Cox-regression analysis with time-dependent variables, propensity score matching and the use of an instrumental variable (facility-level analysis) were used. RESULTS: After adjustments using three different multivariate models, patients treated with high-flux membranes showed a lower all-cause and cardiovascular mortality risks {hazard ratio (HR) = 0.76 [95% confidence interval (CI) 0.61-0.96] and HR = 0.61 (95% CI 0.42-0.87), respectively}, that remained significant after matching by propensity score for all-cause mortality (HR = 0.69, 95% CI 0.52-0.93). However, a facility-level analysis showed no association between the case-mix-adjusted facility percentage of patients dialysed with high-flux membranes and all-cause and cardiovascular mortality. CONCLUSIONS: High-flux dialysis was associated with a lower relative risk of all-cause and cardiovascular mortality. However, dialysis facilities using these dialysis membranes to a greater extent did not show better survival.

Removal of middle molecules with medium cutoff dialyzer in patients on short frequent hemodialysis.

INTRODUCTION: Medium cutoff (MCO) membranes for hemodialysis (HD) remove more effectively large middle molecules than high-flux (HF) membranes. In patients on in-center short frequent HD regimen (5 sessions per week, 2 hours and 30 minutes per session) the effect of MCO on middle weight uremic toxins has not been elucidated. METHODS: This retrospective study included 15 patients previously performing short frequent HD with HF dialyzer (HF-HD), that were switched to short frequent HD with MCO dialyzer (MCO-HD) for 2 months, and returned to HF-HD. The primary endpoint was the predialysis concentration of α1-acid glycoprotein during the different study phases. Secondary endpoints were predialysis concentration of other middle molecules, albumin, and assessment of the quality of life using the 36-item short-form health survey (SF-36). FINDINGS: During MCO-HD phase there was a reduction in mean ± SD α1-acid glycoprotein concentration (98.71 ± 25.2 vs. 88.6 ± 24.6 mg/dL, P = 0.107), followed by an increment 2 months after returning to HF-HD (89.18 ± 26.12 vs. 97.33 ± 31.29 mg/dL, P = 0.002); however, only the second variation was statistically significant. MCO-HD provided lower median predialysis concentration of prolactin (16 [10.2-25.6] vs. 14.1 [11.7-34.8] ng/mL, P = 0.036). Single-pool Kt/V, standard Kt/V, predialysis ß2-microglobulin, myoglobin, and SF-36 questionnaire remained stable during the first two phases (pre-MCO and MCO). ß2-Microglobulin increased in the post-MCO phase (20.02 ± 8.14 vs. 21.27 ± 7.64 µg/mL, P = 0.000). Mean predialysis concentration of albumin reduced significantly from pre-MCO vs. MCO phases (39.9 ± 3.7 vs. 38.3 ± 3.3 g/L, P = 0.020) and rebounded significantly from MCO vs. post-MCO phases (38.7 ± 3.1 vs. 41.3 ± 3.0 g/L, P = 0.007). DISCUSSION: In this retrospective analysis, short frequent MCO-HD promotes a reduction in prolactin, a middle weight uremic toxin, and trends toward a reduction in α1-acid glycoprotein. No patients developed hypoalbuminemia. These findings are encouraging and deserve investigation in prospective studies.

Toxin Removal and Inflammatory State Modulation during Online Hemodiafiltration Using Two Different Dialyzers (TRIAD2 Study).

Uremic toxins play a pathological role in atherosclerosis and represent an important risk factor in dialysis patients. Online hemodiafiltration (HDF) has been introduced to improve the clearance of middle- and large-molecular-weight solutes (>500 Da) and has been associated with reduced cardiovascular mortality compared to standard hemodialysis. This non-randomized, open-label observational study will explore the efficacy of two dialyzers currently used for online HDF, a polysulfone-based high-flux membrane, and a cellulose triacetate membrane, in hemodialysis patients with signs of middle-molecule intoxication or intradialytic hypotension. In particular, the two filters will be evaluated for their ability in uremic toxin removal and modulation of inflammatory status. Sixteen subjects in standard chronic bicarbonate hemodialysis requiring a switch to online HDF in view of their clinical status will be enrolled and divided into two treatment arms, according to the previous history of hypersensitivity to polysulfone/polyethersulfone dialysis filters and hypersensitivity to drugs or other allergens. Group A will consist of 16 patients without a previous history of hypersensitivity and will be treated with a polysulfone filter (Helixone FX100), and group B, also consisting of 16 patients, with a previous history of hypersensitivity and will be treated with asymmetric triacetate (ATA; SOLACEA 21-H) dialyzer. Each patient will be followed for a period of 24 months, with monthly assessments of circulating middle-weight toxins and protein-bound toxins, markers of inflammation and oxidative stress, lymphocyte subsets, activated lymphocytes, and monocytes, cell apoptosis, the accumulation of advanced glycation end-products (AGEs), variations in arterial stiffens measured by pulse wave velocity (PWV), and mortality rate. The in vitro effect on endothelial cells of uremic serum collected from patients treated with the two different dialyzers will also be investigated to examine the changes in angiogenesis, cell migration, differentiation, apoptosis and proliferative potential, and gene and protein expression profile. The expected results will be a better awareness of the different effects of polysulfone gold-standard membrane for online HDF and the new ATA membrane on the removal of uremic toxins removal and inflammation due to blood-membrane interaction.

Rationale for Medium Cutoff Membranes in COVID-19 Patients Requiring Renal Replacement Therapy.

The current pandemic of coronavirus disease 2019 (COVID-19) spotlighted the vulnerability of patients with chronic kidney disease stage 5 on maintenance hemodialysis (HD) to the viral infection. Social distancing is the most effective preventive measure to reduce the risk of infection. Nonetheless, the necessity to frequently reach the dialysis center and the inherent social gathering both impede social distancing and also self-quarantine for infected individuals. A baseline hyperinflammatory state driven by factors such as the retention of uremic toxins afflicts these patients. Concomitantly, a condition of relative immunosuppression is also attributed to similar factors. The use of high-flux (HF) dialyzers for HD is the standard of care. However, with HF membranes, the removal of large middle molecules is scant. Medium cutoff (MCO) dialyzers are a new class of membranes that allow substantial removal of large middle molecules with negligible albumin losses. Recent trials confirmed long-term safety and long-term sustained reduction in the concentration of large uremic toxins with MCO dialyzers. Herein, we discuss the rationale for applying MCO membranes in COVID-19 patients and its possible immunoadjuvant effects that could mitigate the burden of COVID-19 infection in dialysis patients. We also discuss the direct cytopathic effect of the virus on renal tissue and extracorporeal blood purification techniques that can prevent kidney damage or reduce acute kidney injury progression.

[Middle-molecule uremic toxins: A renewed interest]. / Toxines urémiques de moyen poids moléculaire : un véritable regain d'intérêt.

Cardiovascular mortality in patients with chronic kidney disease remains a major problem. The uremic toxins among which the molecules of middle molecular weight are counted contribute significantly to this high mortality, alongside the traditional risk factors. They generate and maintain a chronic inflammatory state called low-level chronic inflammatory state. A growing interest in these molecules has been noted for some years and the uremic toxins associated with this cardiovascular mortality are currently identified: FGF23, cytokines, pentraxin-3 and recently light chains. The existence of an interaction between uremic toxins, inflammation and/or oxidative stress and cardiovascular mortality is well reported in the various epidemiological studies. While the use of anti-oxidative therapies and/or antibodies against uremic toxins or their site of action have not yet yielded a real benefit, hopes are turning to the use of new hemodialysis membranes medium cut-off (MCO), which have the advantage of purifying the uremic toxin middle molecules without a significant loss of albumin. However, additional works are needed to demonstrate the use of these membranes will lead to modulate the morbi-mortality in the dialysis patients.

Analytical and Finite Element Modeling of Nanomembranes for Miniaturized, Continuous Hemodialysis.

Hemodialysis involves large, periodic treatment doses using large-area membranes. If the permeability of dialysis membranes could be increased, it would reduce the necessary dialyzer size and could enable a wearable device that administers a continuous, low dose treatment of chronic kidney disease. This paper explores the application of ultrathin silicon membranes to this purpose, by way of analytical and finite element models of diffusive and convective transport of plasma solutes during hemodialysis, which we show to be predictive of experimental results. A proof-of-concept miniature nanomembrane dialyzer design is then proposed and analytically predicted to clear uremic toxins at near-ideal levels, as measured by several markers of dialysis adequacy. This work suggests the feasibility of miniature nanomembrane-based dialyzers that achieve therapeutic levels of uremic toxin clearance for patients with kidney failure.

Assessment of subjective and hemodynamic tolerance of different high- and low-flux dialysis membranes in patients undergoing chronic intermittent hemodialysis: a randomized controlled trial.

Clinical experience and experimental data suggest that intradialytic hemodynamic profiles could be influenced by the characteristics of the dialysis membranes. Even within the worldwide used polysulfone family, intolerance to specific membranes was occasionally evoked. The aim of this study was to compare hemodynamically some of the commonly used polysulfone dialyzers in Switzerland. We performed an open-label, randomized, cross-over trial, including 25 hemodialysis patients. Four polysulfone dialyzers, A (Revaclear high-flux, Gambro, Stockholm, Sweden), B (Helixone high-flux, Fresenius), C (Xevonta high-flux, BBraun, Melsungen, Germany), and D (Helixone low-flux, Fresenius, Bad Homburg vor der Höhe, Germany), were compared. The hemodynamic profile was assessed and patients were asked to provide tolerance feedback. The mean score (±SD) subjectively assigned to dialysis quality on a 1-10 scale was A 8.4 ± 1.3, B 8.6 ± 1.3, C 8.5 ± 1.6, D 8.5 ± 1.5. Kt/V was A 1.58 ± 0.30, B 1.67 ± 0.33, C 1.62 ± 0.32, D 1.45 ± 0.31. The low- compared with the high-flux membranes, correlated to higher systolic (128.1 ± 13.1 vs. 125.6 ± 12.1 mmHg, P < 0.01) and diastolic (76.8 ± 8.7 vs. 75.3 ± 9.0 mmHg; P < 0.05) pressures, higher peripheral resistance (1.44 ± 0.19 vs. 1.40 ± 0.18 s × mmHg/mL; P < 0.05) and lower cardiac output (3.76 ± 0.62 vs. 3.82 ± 0.59 L/min; P < 0.05). Hypotension events (decrease in systolic blood pressure by >20 mmHg) were 70 with A, 87 with B, 73 with C, and 75 with D (P < 0.01 B vs. A, 0.05 B vs. C and 0.07 B vs. D). The low-flux membrane correlated to higher blood pressure levels compared with the high-flux ones. The Helixone high-flux membrane ensured the best efficiency. Unfortunately, the very same dialyzer correlated to a higher incidence of hypotensive episodes.

Dialysis membrane: from convection to adsorption.

Although patients undergoing dialysis have a complex illness, there are compelling reasons to believe that the inadequate removal of organic waste is an important contributing factor to the illness itself. This paper focuses on the transport phenomena that occur within a dialyser. An attempt is made to clarify how transport phenomena are related to the performance of a dialysis session and how they depend on the membrane characteristics. Our study offers some discussion points on the complex issue of defining what the best parameters could be in comparing the efficiency of different membranes. The new high-flux dialysers have improved larger-molecule clearance and biocompatibility. Membrane performance is a very hard process to evaluate, and different membranes can only be compared by establishing adequate points of comparison. At the same time, the points of comparison themselves may change depending on the type of co-morbidities of the specific patient who is considered for membrane selection. This editorial (together with all the papers presented in this issue) seeks to focus on the membrane's own merits in improving the dialysis therapy.