Medium chain fatty acids are potent binding competitors to improve protein-bound uremic toxin clearance during hemodialysis.

INTRODUCTION

Protein-bound uremic toxins (PBUTs) remain a concerning burden in patients with kidney failure since their removal during hemodialysis is limited due to their tight binding to albumin. Here, we tested whether medium chain fatty acids (MCFAs), potent ligands of human serum albumin (HSA), could be used as binding competitors of PBUTs to increase their removal during a hemodialysis session.

METHODS

A simulated hemodialysis session was performed using bovine blood spiked with PBUTs in the presence of various MCFAs. Blood was sampled serially to measure the concentrations of PBUTs indoxyl sulfate (IS) and p-cresyl sulfate (p-CS).

RESULTS

The binding of MCFAs to HSA was investigated in silico and using fluorescent probe displacement. The free fraction of IS and p-CS were measured after ultrafiltration of HSA solutions and uremic plasma in the presence of MCFAs (0.25-3 mmol/L). Among the four MCFAs tested, octanoate and decanoate were the most prone to interact with HSA Sudlow site II, one of two main binding sites on HSA. The in vitro incubation of HSA solutions and uremic plasma with MCFAs increased the free fraction of IS and p-CS. The per-dialytic infusion of octanoate significantly improved the fractional removal of p-CS from 38% to 88% and IS from 36% to 91%.

CONCLUSIONS

MCFAs can effectively compete with PBUTs for binding to HSA. The per-dialytic administration of octanoate, which strikingly increased the removal of PBUTs, could constitute an efficient and cost-effective strategy to improve the possible clearance of these compounds and prevent their accumulation in patients with kidney failure.