High flux mixed matrix membrane with low albumin leakage for blood plasma detoxification

Dimitrios Stamatialis,Dooli Kim

doi:10.1016/j.memsci.2020.118187

Abstract

Current hemodialysis (HD) therapy removes well small sized toxins but removes less effectively middle molecules and protein-bound uremic toxins (PBUTs). This limited removal has been associated to high mortality of patients due to increased cardiovascular events. The hemodiafiltration therapy, which combines diffusive and convective transport using high flux membranes, can achieve higher removal of middle molecules. However, still the removal of PBUT is limited. Our earlier studies showed that combination of filtration and adsorption on one hollow fiber membrane, so called mixed matrix membranes (MMMs) can achieve removal of range of toxins, including PBUTs, however, these MMMs either had low flux and therefore were not suitable for convective therapies or had high flux but also albumin leakage which is undesired for the HD therapies. In this work, we present for the first time a new generation of MMM which combines high water flux with high albumin retention and very low total protein adsorption and protein leakage. The membrane fabrication conditions are optimized for achieving fibers with small diameter and optimal distribution of the sorbent particles leading to superior removal of PBUT from human plasma, in comparison to the previous MMMs, as well as, to series of commercial membranes used currently in the clinic.

Highlights

Since the first successful renal replacement therapy, developed by Kolff in 1940s [1,2,3], hemodialysis (HD) is considered as the most successful therapy for prolonging the life of patients with end-stage renal disease (ESRD)
The European Uremic Toxin Work Group (EUTox) of the European Society for Artificial Organs (ESAO) suggests that the artificial kidney should remove a range of sizes of uremic toxins [4]: small sized and water soluble [(Mw < 500 g molÀ 1, such as urea (60 g molÀ 1), creatinine (113 g molÀ 1)]; middle sized [(Mw > 500 g molÀ 1, such as β2-microglobulin (11 800 g molÀ 1), parathyroid hormone (9225 g molÀ 1)]; and protein-bound uremic toxins [PBUTs, such as indoxyl sulfate (IS, 251 g molÀ 1), p-cresol sulfate hippuric acid (HA, 179 g molÀ 1) etc
As healthy kidney processes the blood for 24 h, more frequent and prolonged blood purification treatment can achieve better removal of the middle-sized and PBUTs, too

Summary

Introduction

Since the first successful renal replacement therapy, developed by Kolff in 1940s [1,2,3], hemodialysis (HD) is considered as the most successful therapy for prolonging the life of patients with end-stage renal disease (ESRD). Most HD membranes have almost similar or even better performance on the clearance of small-sized toxins compared to the healthy kidney. They have poor performance on removing the middle sized uremic toxins and the PBUTs [8]. The latter are associated to increased risk of cardiovascular events and mortality [9,10,11] and should be removed. As healthy kidney processes the blood for 24 h, more frequent and prolonged blood purification treatment can achieve better removal of the middle-sized and PBUTs, too. There, the membrane modules size should be minimized and the toxin removal should be significantly improved

Methods

Results

Conclusion