title: 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.
authors: Medizinische Klinik IV, Charité-Universitätsmedizin Berlin CBF, D-12200 Berlin, Germany.
authors: Falko
authors: F
authors: Brettschneider
authors: Markus
authors: M
authors: Tölle
authors: Markus
authors: M
authors: von der Giet
authors: Jutta
authors: J
authors: Passlick-Deetjen
authors: Sonja
authors: S
authors: Steppan
authors: Mirjam
authors: M
authors: Peter
authors: Vera
authors: V
authors: Jankowski
authors: Alfred
authors: A
authors: Krause
authors: Sophie
authors: S
authors: Kühne
authors: Walter
authors: W
authors: Zidek
authors: Joachim
authors: J
authors: Jankowski
mesh_terms: D000327:Adsorption; D001798:Blood Proteins / Q000378:metabolism; D003408:Cresols / Q000097:blood / Q000302:isolation & purification* / Q000378:metabolism; D006801:Humans; D007200:Indican / Q000097:blood / Q000302:isolation & purification* / Q000378:metabolism; D010648:Phenylacetates / Q000097:blood / Q000302:isolation & purification* / Q000378:metabolism; D010865:Pilot Projects; D010956:Plasmapheresis / Q000379:methods*; D011485:Protein Binding; D006435:Renal Dialysis / Q000379:methods*; D013463:Sulfuric Acid Esters / Q000097:blood / Q000302:isolation & purification* / Q000378:metabolism; D014511:Uremia / Q000097:blood / Q000378:metabolism / Q000628:therapy*
chemical_list: D001798:Blood Proteins; D003408:Cresols; D010648:Phenylacetates; D013463:Sulfuric Acid Esters; C408690:4-cresol sulfate; C025136:phenylacetic acid; D007200:Indican