A tRial Evaluating Mid Cut-Off Value Membrane Clearance of Albumin and Light Chains in HemoDialysis Patients: A Safety Device Study

Abstract

Background: A new class of dialysis membrane, the mid cutoff (MCO) dialyzer, has been developed to improve the clearance of uremic toxins in hemodialysis (HD). The a tRial Evaluating Mid cutOff Value membrane clearance of Albumin and Light chains in HemoDialysis patients (REMOVAL-HD) study aimed to determine if regular use of MCO dialyzer was safe and specifically did not result in a significant loss of albumin. Methods: This investigator initiated, crossover, longitudinal , device study was conducted across 9 centers in Australia and New Zealand (n = 89). Participants had a 4-week wash-in with high-flux HD, followed by 24-week intervention with MCO HD and a subsequent 4-week wash-out with high-flux HD. The primary outcome was change in serum albumin between weeks 4 and 28. Secondary outcomes included trends in serum albumin, changes in kappa-and lambda-free light chains (FLC), 6-min walk test (6MWT), malnutrition inflammation score (MIS), restless legs score and quality of life. Results: Participants had a mean age of 66 ± 14 years, 62% were men, 45% were anuric, and 51% had diabetes. There was no reduction in serum albumin following treatment with MCO HD (mean reduction-0.7 g/L, 95% CI-1.5 to 0.1). A sustained, unexplained reduction in serum REMOVAL-HD Study 469

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

“…Uniformly with our findings, two other recent trials de­monstrated a reduction in the concentration of FLC [28, 35]. One of the studies was similar in design to ours: a randomized, open-label, cross-over study, with 40 patients who were divided to carry out 3 months of MCO-HD followed by 3 months of HF-HD, or vice versa [35].…”

“…Extracorporeal techniques can be helpful in the modulation of an immune dysregulated response, both in the severely ill and in the chronic HD patient. Recent clinical trials demonstrated consistent results regarding the application of MCO membranes in patients on maintenance HD [28, 31, 35]. These trials confirmed long-term safety and long-term sustained reductions in the concentrations of large uremic toxins, cytokines, and FLC with MCO-HD when compared to conventional HF-HD.…”

“…The primary concern about safety mainly related to albumin losses has been overcome. Higher removal of middle molecules has been consistently seen in recent trials [28, 31, 35]. The application of MCO membranes in patients currently undergoing HF-HD could potentially reduce the incidence of infections.…”

“…MCO membranes present a significantly improved sieving curve compared to high-flux (HF) membranes and a high retention onset value. At the same time, they display a significantly lower albumin loss than high cutoff membranes, allowing for safe and long-term applications [28]. These characteristics represent a phenomenal compromise to obtain the desired therapeutic target in COVID-19 patients both for chronic dialysis continuation and for application in CRRT.…”

“…The other study, REMOVAL-HD [28], was a multicenter, open-label, non-randomized, single-arm trial with 89 individuals assigned to receive 4 weeks of HF-HD as wash-in, then 24 weeks of MCO-HD, and finally 4 weeks of HF-HD as wash-out. The primary endpoint was change in pre-dialysis serum albumin concentration before and after 6 months of MCO-HD.…”