Removal of Protein‐Bound, Hydrophobic Uremic Toxins by a Combined Fractionated Plasma Separation and Adsorption Technique

Abstract

Protein-bound uremic toxins, such as phenylacetic acid, indoxyl sulfate, and p-cresyl sulfate, contribute substantially to the progression of chronic kidney disease (CKD) and cardiovascular disease (CVD). However, based on their protein binding, these hydrophobic uremic toxins are poorly cleared during conventional dialysis and thus accumulate in CKD-5D patients. Therefore, we investigated whether hydrophobic and cationic adsorbers are more effective for removal of protein-bound, hydrophobic uremic toxins than conventional high-flux hemodialyzer. Five CKD-5D patients were treated using the fractionated plasma separation, adsorption, and dialysis (FPAD) system for 5 h. A control group of five CKD patients was treated with conventional high-flux hemodialysis. Plasma concentrations of phenylacetic acid, indoxyl sulfate, and p-cresyl sulfate were measured. Removal rates of FPAD treatment in comparison to conventional high-flux hemodialysis were increased by 130% for phenylacetic acid, 187% for indoxyl sulfate, and 127% for p-cresol. FPAD treatment was tolerated well in terms of clinically relevant biochemical parameters. However, patients suffered from mild nausea 2 h after the start of the treatment, which persisted until the end of treatment. Due to the high impact of protein-bound, hydrophobic uremic toxins on progression of CKD and CVD in CKD-5D patients, the use of an adsorber in combination with dialysis membranes may be a new therapeutic option to increase the removal rate of these uremic toxins. However, larger, long-term prospective clinical trials are needed to demonstrate the impact on clinical outcome.

Enhanced Indoxyl Sulfate Dialyzer Clearance with the Use of Binding Competitors

“…With an appropriate displacer, the removal of indoxyl sulfate can be increased up to 3 times compared to baseline removal. Similar efficiency of improved indoxyl sulfate removal was observed only in methods utilizing sorbent technologies [38][39][40] . A 2.4-fold increase of indican (indoxyl sulfate) removal was reported by Meyer et al when adding activated carbon into the dialysate in an in vitro HD model [39] .…”

“…A 2.4-fold increase of indican (indoxyl sulfate) removal was reported by Meyer et al when adding activated carbon into the dialysate in an in vitro HD model [39] . A fractionated plasma separation and adsorption technique (FPSA) showed a 2.9-fold increase of whole body indoxyl sulfate removal in a 4-hour treatment [40] . For a comparison of indoxyl sulfate removal between our method and other renal replacement therapy modalities, see [25] .…”

Interaction of Proteins with Polyelectrolytes: Comparison of Theory to Experiment

“…Moreover, small charged molecules as, e.g., phenylacetic acid or indoxylsulfate present toxins that adhere to blood proteins such as human serum albumin. [66][67][68][69] Full removal of these toxins by dialysis presents a central and urgent problem of modern nephrology. 68 Precise thermodynamic information on the binding process is the experimental prerequisite for a detailed understanding of the interaction of proteins with polyelectrolytes.…”

A possible link between polyunsaturated fatty acids and uremic toxins from the gut microbiota in hemodialysis patients: A hypothesis

“…31,32 Currently, sorbents and nonpharmacological therapies are promising strategies. 33 Indeed, in an in vitro HD model, Meyer et al 34 observed a 2.4-fold increase in the IS removal rate when a sorbent (activated carbon) was added to the dialysate.…”