Biological testing unification for hemodialysis membranes evaluation: A step towards standardization

Abstract

Current hemodialysis treatments can cause adverse effects, many of which are linked to the membranes used in the process. These issues are being addressed through new materials and technologies, making it urgent to establish minimum guidelines for evaluating such membranes. This review proposes standardizing the biological tests and variables to evaluate the performance of new membranes, aiming to replicate hemodialysis conditions closely. The tests were categorized into protein adsorption, protein transmission, platelet adhesion, platelet activation, blood coagulation times, hemolysis, complement activation, and cytotoxicity. For protein adsorption, static tests are recommended as an initial step to rule out membrane adhesion, followed by dynamic tests that must be conducted using a crossflow system (>250 mL/min flow) and a solution mimicking real conditions (BSA, lysozyme, trypsin, pepsin, creatinine, urea, albumin, fibrinogen, and γ-globulin). Protein transmission tests must employ dynamic conditions, using human blood or platelet-rich plasma for a minimum time of 3.5 h. Complement activation should be tested using human blood and ELISA assays to detect C3, C5 TCC, and SC5b-9. Blood coagulation times (APTT, TT, FT, TCT, and TAT) should be measured with platelet-poor and platelet-rich plasma. Hemolysis tests should transition from water bath to continuous mode for at least 3.5 h. Cytotoxicity tests should compare the MTT assay with other methods (Alamar Blue, Lactate Dehydrogenase Assay, Flow Cytometry, or Trypan Blue Exclusion Test) and use different cell types for comprehensive validation. By implementing these minimum biological tests, membrane evaluations would more accurately reflect the real-world applications, ensuring biocompatibility, effectiveness, and efficiency.