In vitro Study of Removal of Protein-Bound Toxins

Abstract

Protein-bound toxins are not efficiently removed by conventional hemodialysis techniques. In order to improve the removal of protein-bound toxins, we performed an in vitro study to evaluate the effects of dilution and pH change on the dissociation of protein-bound toxins from albumin. Human plasma harvested by therapeutic apheresis treatment was diluted with saline or isotonic NaHCO₃ solution, and the amounts of the free fractions of indoxyl sulfate (IS) and homocysteine were determined. The results suggested that IS was dissociated easily from albumin by dilution and pH change; higher dilution was associated with more effective removal and a greater increase of the free fraction of IS. However, these methods did not facilitate dissociation of homocysteine from albumin. Effective removal of some protein-bound toxins may be achieved by applying dilution and pH change methods to blood purification techniques, such as pre-dilution on-line hemodiafiltration.

Facile one-pot synthesis of magnetic nitrogen-doped porous carbon for high-performance bilirubin removal from BSA-rich solution

“…However, it should be noted that these experiments of bilirubin adsorptions on various pure porous carbons are mostly conducted in albumin-free solution, which is contrary to the facts that serum albumin is the most abundant protein in blood and bilirubin exists primarily in the form of albumin-bilirubin complex. [13][14][15] Despite the advantage of high effectiveness for free bilirubin removal, these pure porous carbon adsorbents usually perform poorly on the removal of albumin-bonded bilirubin. For instance, the reported adsorption capacity of carbon nanotube sheets toward bovine serum albumin (BSA)-bonded bilirubin is 9.7 mg g À1 , which is signicantly lower than the values obtained for free bilirubin removal.…”

Dialysate With High Dissolved Hydrogen Facilitates Dissociation of Indoxyl Sulfate From Albumin

“…The concentration of IS was determined by high performance liquid chromatography. Free fractions (FR) were calculated as below formula ( 4 ).…”

“…Therefore, it might be better if IS is dissociated from albumin and excluded during HD therapy. Yamamoto, et al demonstrated in vitro that dilution and pH change of dialysate facilitate IS dissociate from albumin ( 4 ). The predilution mode can dilute the blood before hemodia filter in on-line HDF therapy.…”

Uremic Retention Solutes

“…Another area of research concerns altering the dialysis milieu in order to affect the binding of URS to plasma proteins. Examples of this effort which have data supporting their use include using hypertonic solution, the use of albumin-binding site competitors such as tryptophan and docosahexaenoic acid, increasing temperature, plasma dilutions, and pH manipulation of the dialysate [47,[90][91][92][93][94].…”