An In Vitro System for Studying Toxin Transport Across Hemodialysis Membranes

Healthy kidneys regulate acid-base balance and electrolytes, produce hormones, and clear excess fluids and uremic toxins. Progressive kidney function loss in chronic kidney disease leads to end-stage kidney disease (ESRD), where fluid and toxin accumulation causes severe complications and can be fatal. ESRD requires renal replacement therapy; kidney transplantation is preferred; however, limited availability of donor organs makes hemodialysis (HD) the most used treatment option. In the last years, many studies had focused on development of new membranes with improved toxin removal, however, these studies implement various experimental conditions making direct comparison between membranes challenging. Here, we develop an in vitro system for evaluating various membranes.

We performed toxin transport studies using commercially available hollow fiber membranes (FX1000, Fresenius) as well as newly developed mixed matrix membrane (MMM) hollow fibers, both assembled in a mini dialyzer. Creatinine (Cr), hippuric acid (HA) and indoxyl sulfate (IS) were used as model uremic toxins and their removal by the membranes from human plasma and full human blood under a range of experimental conditions was studied.

We mainly implemented dialysate recirculation, which allowed for monitoring of the mass balance of toxins inside the mini dialyzer and for obtaining better understanding about the membrane fouling and concentration polarization phenomena. Dialysance normalized by membrane effective area was used as a key parameter for assessing the performance of the membranes.

Our findings are in good agreement to various literature studies for small and larger scale dialyzers suggesting that the proposed in vitro system can be used for comparison of membranes for HD.