No abstract

Substantial activation of platelets can occur in the course of hemodialysis. Platelet surface markers show evidence of platelet degranulation. Some activation occurs due to exposure of blood to the roller pump segment and microbubbles may play a role. Platelet activation seems to be reduced with reused dialyzers or with those containing synthetic versus cellulosic membranes. Nevertheless, a substantial degree of platelet activation can be demonstrated with polysulfone and other synthetic membranes; the amount of activation may differ substantially among polysulfone membranes, depending on the manufacturer and the polyvinylpyrrolidone content. Platelet-platelet and platelet-leukocyte aggregates have been detected in the dialyzer blood outflow line and the consequences of these to the microcirculation are unknown. Typically, the platelet count decreases slightly during the first hour of dialysis, but mostly returns to initial values by the end of dialysis. A number of chronic hemodialysis patient cases have been reported in which a marked decrease in platelet count (50% or more) during dialysis was observed, resulting in mild degrees of predialysis thrombocytopenia. In only one case was the decrease in platelet count associated with bleeding. Dialyzer hypersensitivity symptoms are infrequently associated with a fall in platelet count. Most recent cases of dialysis-associated thrombocytopenia have been with polysulfone membranes, especially polysulfone membranes sterilized by electron beam. The exact cause of these reactions remains unknown.

Background and objectivesExpanded hemodialysis therapy enabled by medium cut-off membranes may promote greater clearance of larger middle molecules that comprise putative uremic solutes than conventional high-flux dialysis. This randomized trial evaluated the efficacy and safety of hemodialysis treatment with a medium cut-off dialyzer.Design, setting, participants, & measurementsClinically stable patients on maintenance hemodialysis were randomized to receive dialysis with either a medium cut-off dialyzer (Theranova 400) or a high-flux dialyzer (Elisio-17H) over 24 weeks of treatment. The primary safety end point was the predialysis serum albumin level after 24 weeks of treatment. The primary efficacy end point was the reduction ratio of free λ light chains at 24 weeks of treatment.ResultsAmong 172 patients on maintenance hemodialysis, mean age was 59±13 years, 61% were men, 40% were Black, and mean dialysis vintage was 5±4 years. Of the 86 patients randomized to each dialyzer, 65 completed the trial in each group. The reduction ratio for the removal of free λ light chains was significantly higher in the Theranova 400 group compared with the Elisio-17H group after 4 weeks (39% versus 20%) and 24 weeks (33% versus 17%; both P<0.001). Among secondary end points, the Theranova 400 group demonstrated significantly larger reduction ratios at 4 and 24 weeks for complement factor D, free κ light chains, TNFα, and β2-microglobulin (P<0.001 for all), but not for IL-6. Predialysis serum albumin levels were similar between groups after 24 weeks (4 g/dl with the Theranova 400 and 4.1 g/dl with the Elisio-17H), consistent with noninferiority of the Theranova 400 dialyzer in maintaining predialysis serum albumin levels after 24 weeks of treatment.ConclusionsHemodialysis therapy with the Theranova 400 dialyzer provides superior removal of larger middle molecules, as exemplified by free λ light chains, compared with a similar size high-flux dialyzer, while maintaining serum albumin level.Clinical Trial registry name and registration numberA Multi-Center, Prospective, Randomized, Controlled, Open-Label, Parallel Study to Evaluate the Safety and Efficacy of the Theranova 400 Dialyzer in End Stage Renal Disease (ESRD) Patients, NCT03257410.

Kidney failure is an important outcome for patients, clinicians, researchers, healthcare systems, payers, and regulators. However, no harmonized international consensus definitions of kidney failure and key surrogates of progression to kidney failure exist specifically for clinical trials. The International Society of Nephrology convened an international multistakeholder meeting to develop consensus on this topic. A core group, experienced in design, conduct, and outcome adjudication of clinical trials, developed a database of 64 randomized trials and the 163 included definitions relevant to kidney failure. Using an iterative process, a set of proposed consensus definitions were developed and subsequently vetted by the larger multi-stakeholder group of 83 participants representing 18 different countries. The