Abstract
Removal of protein-bound uremic toxins (PBUTs) during conventional dialysis is insufficient. PBUTs are associated with comorbidities and mortality in dialysis patients. Albumin is the primary carrier for PBUTs and only a small free fraction of PBUTs are dialyzable. In the past, we proposed a novel method where a binding competitor is infused upstream of a dialyzer into an extracorporeal circuit. The competitor competes with PBUTs for their binding sites on albumin and increases the free PBUT fraction. Essentially, binding competitor-augmented hemodialysis is a reactive membrane separation technique and is a paradigm shift from conventional dialysis therapies. The proposed method has been tested in silico, ex vivo, and in vivo, and has proven to be very effective in all scenarios. In an ex vivo study and a proof-of-concept clinical study with 18 patients, ibuprofen was used as a binding competitor; however, chronic ibuprofen infusion may affect residual kidney function. Binding competition with free fatty acids significantly improved PBUT removal in pre-clinical rat models. Based on in silico analysis, tryptophan can also be used as a binding competitor; importantly, fatty acids or tryptophan may have salutary effects in HD patients. More chemoinformatics research, pre-clinical, and clinical studies are required to identify ideal binding competitors before routine clinical use.
Highlights
Uremic toxins have broadly been classified into three categories: (1) small-sized toxins (500 Da), and (3) protein-bound uremic toxins (PBUTs) [1]
Key Contribution: This review provides a comprehensive summary of current evidence in support of binding competition as a potential method to improve protein-bound uremic toxin removal during hemodialysis
Ttlheetssetpreraomces.sTeshaerferamcteionnaballerteomqouvanatlitoaftiIvSewanaaslyesxispsrienscseepdraostetinh–edarmugobuindt ipnegrauf-nit of time finleitayvdinagtatahree daviaaliylasbalteefoorumtleotstadsraugpceorcmepnotaugnedso[f1t5h].e amount per unit of time entering at the blood inleEt.qWuathioenn1in: fPursoitneginp−htoosxpinha+teDbruufgfer↔soPlurottieoinn −(PDBrSu)gw+ithToouxitnany add(1e)d binding competitor, indoxyl sulfate (IS) removal was 10.2%, which improved to 18.5% with TRP and to 27.7% with docosahexaenoic acid (DHA) added to theEiqnufautsioionn2.: SPirnocteeitnh−e btoixnidnin↔g aPffironteitiyn o+f DTHoxAinto albumin (1.0(2×) 107 M−1) is much higher than that of TPrRoPteitno−alDbruumg i↔n (1P.r0ot×ein10+4 MDr−u1g) [16], DHA is the stronger binding competitor of the two and leads to a larger improvement in dialytic removal of IS
Summary
Uremic toxins have broadly been classified into three categories: (1) small-sized toxins (500 Da), and (3) protein-bound uremic toxins (PBUTs) [1]. Note that the negative reduction ratio of CMPF does not suggest that there is an increase in CMPF generation rate due to dialysis; rather, it is an indication of the fact that protein concentration (and bound CMPF) is increased due to ultrafiltration. To remove this class of toxin, we proposed a method where PBUTs can be removed by competitive binding, known as the displacer method [12,13]. We provide a brief discussion of the other technologies that aim to improve PBUT removal and conclude with thoughts on the steps to make this concept a clinical reality
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
