Protein Loss With High-Flux and Medium Cut-Off Membranes: An Ex Vivo Comparative Analysis

Removal of middle-sized uremic toxins is one goal of hemodialysis. However, dialysis membranes are nonselective, raising the specter that salutary proteins may also be removed. To better understand the spectrum of proteins filtered by medium cut-off (MCO) and high-flux membranes, we conducted quantitative analyses of proteins in ultrafiltrates. We developed an ex vivo system that allows us to concurrently compare two dialyzers under the same conditions, using the same plasma source. We used this system to study the ultrafiltrate protein loss of two high-flux (Fresenius Optiflux F180NRe, USA; Fresenius FX CorAL80, Germany) and one MCO dialyzer (Baxter Theranova 400, Germany). Ultrafiltrates underwent analysis including gel electrophoresis, quantitative proteomics using liquid chromatography-tandem mass spectrometry, and immunoassays. We identified 244 proteins and semiquantified 113 of them, all of which were more prevalent in MCO compared with high-flux ultrafiltrate (MCO/Optiflux: median 8.25-fold; MCO/CorAL: median 9.14-fold). The protein distribution in MCO ultrafiltrate was skewed toward higher molecular mass. Notably, the ultrafiltered proteins include some with putative salutary functions. In conclusion, our data consistently show a higher protein loss with MCO membrane compared with high-flux dialyzers. The extent to which biological functions are impacted by the removal of proteins warrants bioinformatic analyses and clinical studies.