Removal of indoxyl sulfate by water-soluble poly-cyclodextrins in dialysis

Indoxyl sulfate (IS) is a uremic toxin related to the progression of chronic kidney diseases. Removal of IS from the plasma would reduce the risk of cardiovascular disease. In this study, crosslinked poly-β-cyclodextrins (PCDs) were used as a water-soluble adsorbent agent for IS in dialysis for the first time. The molecular weight of PCDs was found to be proportional to the crosslinking time between β-cyclodextrin monomers and epichlorohydrin, yet the proportion of β-cyclodextrin that reacted with epichlorohydrin decreased. It was observed that PCD after 2 h crosslinking yielded the best IS-binding capability in PBS, while reaching the binding equilibrium within 30 min and yielding a maximum binding capability of 45 mg g^-1. Furthermore, the binding mechanism was investigated by two-dimensional nuclear magnetic resonance, Job's plot method, and salt treatments. To simulate the clinical removal of IS we established a macro-dialysis and added PCD obtained from 2 h crosslinking (PCD1) to the dialysate. The removal of plasma IS from the dialysate by PCD1 was about twice as much as that removed from the dialysate without PCD1. Therefore, crosslinked poly-β-cyclodextrins may represent a simple, low-cost, and effective IS removal strategy with great potential for removing other hydrophobic plasma-bound toxins in dialysis. It could also serve as a supplement for the existing non-adsorbent added therapy.