Werner Beck

Performance of hemodialysis with novel medium cut-off dialyzers

Background. Compared to high-flux dialysis membranes, novel medium cut-off (MCO) membranes show greater permeability for larger middle molecules. Methods. In two prospective, open-label, controlled, randomized, crossover pilot studies, 39 prevalent hemodialysis (HD) patients were studied in four dialysis treatments as follows: study 1, three MCO prototype dialyzers (AA, BB and CC with increasing permeability) and one high-flux dialyzer in HD; and study 2, two MCO prototype dialyzers (AA and BB) in HD and high-flux dialyzers in HD and hemodiafiltration (HDF). Primary outcome was lambda free light chain (&lgr;FLC) overall clearance. Secondary outcomes included overall clearances and pre-to-post-reduction ratios of middle and small molecules, and safety of MCO HD treatments. Results. MCO HD provided greater &lgr;FLC overall clearance [least square mean (standard error)] as follows: study 1: MCO AA 8.5 (0.54), MCO BB 11.3 (0.51), MCO CC 15.0 (0.53) versus high-flux HD 3.6 (0.51) mL/min; study 2: MCO AA 10.0 (0.58), MCO BB 12.5 (0.57) versus high-flux HD 4.4 (0.57) and HDF 6.2 (0.58) mL/min. Differences between MCO and high-flux dialyzers were consistently significant in mixed model analysis (each P < 0.001). Reduction ratios of &lgr;FLC were greater for MCO. Clearances of &agr;1-microglobulin, complement factor D, kappa FLC (&kgr;FLC) and myoglobin were generally greater with MCO than with high-flux HD and similar to or greater than clearances with HDF. Albumin loss was moderate with MCO, but greater than with high-flux HD and HDF. Conclusions. MCO HD removes a wide range of middle molecules more effectively than high-flux HD and even exceeds the performance of high-volume HDF for large solutes, particularly &lgr;FLC.

In Vitro Comparative Assessment of Mechanical Blood Damage Induced by Different Hemodialysis Treatments

Abstract Gradual deterioration of red blood cells (RBCs) due to mechanical stress (chronic hemolysis) is unavoidable during treatments that involve extracorporeal blood circulation, such as hemodialysis (HD). This effect is generally undetectable and does not generate any acute symptoms, but it leads to an increase in plasma free hemoglobin (fHb). There are no absolute safety levels for fHb increase, indicating the need for an empirical evaluation using comparative testing. The increase in fHb levels was investigated in vitro by applying double‐needle double‐pump HD (HD‐DNDP), a new modality in which arterial and venous pumps both run continuously. fHb was measured during typical and worst‐case simulated dialysis treatments (double‐needle single‐pump HD [HD‐DNSP], hemodiafiltration [HDF‐DN], single‐needle double‐pump HD [HD‐SNDP], and HD‐DNDP) performed in vitro using bovine blood for 4u2009h. Hemolysis‐related indices (fHb%; index of hemolysis, IH; and normalized IH) were calculated and used for comparison. The increase in fHb during either HDF‐DN or HD‐SNDP with Artis and AK200 dialysis machines was similar, while the fHb at the maximum real blood flow rate (Qbreal) at the completion of the HD‐DNDP treatment on Artis was higher than that for HD‐DNSP using a Phoenix dialysis machine (fHb %u2009=u20091.24u2009±u20090.13 and 0.92u2009±u20090.12 for the Artis machine with HD‐DNDP at Qbrealu2009=u2009450u2009mL/min and Phoenix with HD‐DNSP at Qbrealu2009=u2009500u2009mL/min, respectively). However, the fHb levels increased linearly, and no steep changes were observed. The increases observed during HD‐DNDP were the same order of magnitude as those for widely used bloodlines and treatment modes for delivering dialysis treatments. The observed results matched literature findings, and thus the measured fHb trends are not predicted to have clinical side effects. HD‐DNDP treatment with Artis does not merit any additional concern regarding mechanical stress to RBCs compared with that observed for routinely used dialysis treatments, bloodlines and machines. Although the in vitro measurement of the fHb increase in bovine blood does not allow a prediction of the absolute level of blood mechanical damage or the possible effects in humans, such measurements are valuable for assessing hemolytic harm by performing tests comparing the proposed treatment with existing devices.

Assessment of the association between increasing membrane pore size and endotoxin permeability using a novel experimental dialysis simulation set-up

BackgroundMembranes with increasing pore size are introduced to enhance removal of large uremic toxins with regular hemodialysis. These membranes might theoretically have higher permeability for bacterial degradation products. In this paper, permeability for bacterial degradation products of membranes of comparable composition with different pore size was investigated with a new in vitro set-up that represents clinical flow and pressure conditions.MethodsDialysis was simulated with an AK200 machine using a low-flux, high-flux, medium cut-off (MCO) or high cut-off (HCO) device (nu2009=u20096/type). A polyvinylpyrrolidone-solution (PVP) was recirculated at blood side. At dialysate side, a challenge solution containing a filtrated lysate of two water-borne bacteria (Pseudomonas aeruginosa and Pelomononas saccharophila) was infused in the dialysate flow (endotoxin ≥xa04EU/ml). Blood and dialysate flow were set at 400 and 500xa0ml/min for 60xa0min. PVP was sampled before (PVPpre) and after (PVPpost) the experiment and dialysate after 5 and 55xa0min. Limulus Amebocyte Lysate (LAL) test was performed. Additionally, samples were incubated with a THP-1 cell line (24xa0h) and IL-1β levels were measured evaluating biological activity.ResultsThe LAL-assay confirmed presence of 9.5u2009±u20097.4xa0EU/ml at dialysate side. For none of the devices the LAL activity in PVPpre vs. PVPpost was significantly different. Although more blood side PVP solutions had a detectable amount of endotoxin using a highly sensitive LAL assay in the more open vs traditional membranes, the permeability for endotoxins of the 4 tested dialysis membranes was not significantly different but the number of repeats is small. None of the PVP solutions induced IL-1β in the THP-1 assay.ConclusionsA realisitic in vitro dialysis was developed to assess membrane translocation of bacterial products. LAL activity on the blood side after endotoxin exposure did not change for all membranes. Also, none of the PVPpost solutions induced IL-1β in the THP-1 bio-assay.

Medium Cut-Off Membranes - Closer to the Natural Kidney Removal Function:

Renal failure (RF) is characterized by the loss of the ability of the kidneys to excrete wastes, concentrate urine, conserve electrolytes, and maintain fluid balance. Acute kidney injury can be a life-threatening illness, with a mortality of between 50% and 80% (3). ESRD occurs in the late stages of chronic kidney disease and is associated with an irreversible loss of kidney function. Renal replacement therapy (RRT) replaces kidney function in patients with both types of renal failure. There are 2 possible alternatives to treat chronic RF: organ transplantation or, more commonly, dialysis. However, the natural secretion of kidney hormones, which influences blood pressure, cannot be achieved with dialysis treatment modalities. Over 2 million people worldwide currently receive treatment with dialysis or a kidney transplant to stay alive, yet this number may represent only 10% of people who actually need treatment to live (4). Of the 2 million people who receive treatment for kidney failure, the majority are treated in only 5 countries: the United States, Japan, Germany, Brazil, and Italy. These 5 countries represent only 12% of the world population. Only 20% are treated in approximately 100 developing countries that make up over 50% of the world population (4). In medicine, hemodialysis (HD) is the process of removing blood from a patient, purifying the blood through an artificial kidney (dialyzer), and then returning it to the patient’s bloodstream. On the basis of the developments of Willem Kolff and Nils Alwall in the 1940s, the dialyzer membrane systems have undergone multiple development cycles and are now the basis of an effective, reliable, and cost-effective treatment approach. In the early days of dialysis, large and unwieldy plate dialyzers made of cellulose membranes were used. Until the 1970s, cellulosic membranes were used exclusively and represented the majority of membranes used in hemodialysis worldwide (5). DOI: 10.5301/ijao.5000603

Comparative Effectiveness of Dialyzers: A Longitudinal, Propensity Score-matched Study of Incident Hemodialysis Patients.

Differences in dialyzer design may have consequences for patient outcomes. We evaluated the comparative effectiveness of commonly used dialyzers with respect to measures of dialysis treatment, anemia management, inflammation, and dialyzer clotting. Patients receiving hemodialysis between January 1, 2009, and December 31, 2013, and using polyarylethersulfone–polyvinylpyrrolidone (PAS-PVP; Polyflux Revaclear) or polysulfone (PS; Optiflux 160 or Optiflux 180) dialyzers were followed for 1 year or until end of study or censoring for dialyzer switch, modality change, or loss to follow-up. For each comparison, eligible patients were propensity score-matched 1:1 on a range of baseline characteristics. Outcomes were assessed using generalized linear mixed models. Dialysis adequacy was similar in both dialyzer groups. Erythropoiesis-stimulating agent (ESA) doses were lower for patients using PAS-PVP versus patients using PS-160 (difference range: 75–589 units/treatment; statistically significant in months 1–5 and 7) and for patients using PAS-PVP versus patients using PS-180 (difference range: 27–591 unit/treatment; statistically significant in months 1–9). Intravenous iron doses trended lower for patients using PAS-PVP versus patients using PS, but hemoglobin concentrations were equivalent. In conclusion, use of PAS-PVP versus PS dialyzers was associated with equivalent dialysis adequacy, lower ESA doses, modestly lower Intravenous iron doses, and equivalent hemoglobin concentrations.

Hypoalbuminemia: a price worth paying for improved dialytic removal of middle-molecular-weight uremic toxins?

Hemodiafiltration (HDF) increases the removal of middle-molecular-weight uremic toxins and may improve outcomes in patients with end-stage kidney disease (ESKD), but it requires complex equipment and comes with risks associated with infusion of large volumes of substitution solution. New high-flux hemodialysis membranes with improved diffusive permeability profiles do not have these limitations and offer an attractive alternative to HDF. However, both strategies are associated with increased albumin loss into the dialysate, raising concerns about the potential for decreased serum albumin concentrations that have been associated with poor outcomes in ESKD. Many factors can contribute to hypoalbuminemia in ESKD, including protein energy wasting, inflammation, volume expansion, renal loss and loss into the dialysate; of these factors, loss into the dialysate is not necessarily the most important. Furthermore, recent studies suggest that mild hypoalbuminemia per se is not an independent predictor of increased mortality in dialysis patients, but in combination with inflammation it is a poor prognostic sign. Thus, whether hypoalbuminemia predisposes to increased morbidity and mortality may depend on the presence or absence of inflammation. In this review we summarize recent findings on the role of dialysate losses in hypoalbuminemia and the importance of concomitant inflammation on outcomes in patients with ESKD. Based on these findings, we discuss whether hypoalbuminemia may be a price worth paying for increased dialytic removal of middle-molecular-weight uremic toxins.

Requirements and Pitfalls of Dialyzer Sieving Coefficients Comparisons

Abstract Sieving coefficients reported in dialyzer data sheets and instructions for use (IFUs) indicate the potential of different solutes to pass across a particular membrane. Despite being measured in vitro, sieving coefficient data are often used as a predictor of the clinical performance of dialyzers. Although standards for the measurement of sieving coefficients exist, the stated methodologies do not offer sufficient guidance to ensure comparability of test results between different dialyzers. The aim of this work was to investigate the relationship between sieving coefficients and published clinical performance indicators for two solutes, albumin loss and beta‐2 microglobulin (β2M) reduction ratio (RR), and to assess the impact of different in vitro test parameters on sieving coefficient values for albumin, β2M, and myoglobin. Clinical albumin loss and β2M RR for commercially available dialyzers used in hemodialysis (HD) and post‐dilution hemodiafiltration (HDF) were extracted from the literature and plotted against sieving coefficients reported in data sheets and IFUs. Albumin, β2M, and myoglobin sieving coefficients of a selection of dialyzers were measured per the ISO 8637 standard. The impact of in vitro testing conditions was assessed by changing blood flow rate, ultrafiltration (UF) rate, sampling time, and origin of test plasma. Results showed variation in albumin loss and β2M RR for the same sieving coefficient across different dialyzers in HD and HDF. Changes in blood flow rates, UF rates, sampling time, and test plasma (bovine vs. human) caused marked differences in sieving coefficient values for all investigated solutes. When identical testing conditions were used, sieving coefficient values for the same dialyzer were reproducible. Testing conditions have a marked impact on the measurement of sieving coefficients, and values should not be compared unless identical conditions are used. Further, variability in observed clinical data in part reflects the lack of definition of test conditions.