FP437
ADSORPTION OF HYDROPHOBIC UREMIC TOXINS BY EXTRACORPOREAL ADSORBER PARTICLES

INTRODUCTION AND AIMS: Hydrophobic uremic toxins are accumulating in the blood of patients with chronic kidney disease (CKD) and contribute to the high risk of cardiovascular disease (CVD) in these patients. The removal of hydrophobic uremic toxins from the blood by current dialysis techniques is difficult due to their high binding affinity to plasma proteins. This greatly increases their molecular weight and prevents their removal through the pores of the dialysis membrane. Adsorber techniques be an appropriate alternative and may offer increased uremic toxin removal rates. We developed and investigated an extracorporeal adsorber particle with a modified surface for the adsorption of hydrophobic uremic toxins to improve the existing high-flux hemodialysis techniques.

METHODS: The “Netphob” particle consists of a porous, activated charcoal core with a hydrophobic surface coating of cross-linked polyvinylpyrrolidone. The adsorption capacity of the particles was tested by incubation or perfusion with blood, serum albumin or a buffer solution containing mixtures of hydrophobic uremic toxins as found in the blood of CKD patients stage 5. Bound toxins were quantified by analytical chromatography. The hemocompatibility of the particles was assessed by quantifying the production of the thrombin-antithrombin III complex (TAT) and complement component 5a (C5a) as well as the leukocyte and thrombocyte counts in the blood.

RESULTS: A time-dependent increase in uremic toxin adsorption was depicted and all tested toxins showed a high binding affinity to the “Netphob” particles. The investigation of the hemocompatibility showed no significant increase either in C5a or TAT, or in thrombocyte concentration after incubating blood with the “Netphob” particles, although leucocyte counts were reduced.

CONCLUSIONS: In conclusion, the “Netphob” particle shows a high adsorption capacity to all tested hydrophobic uremic toxins and a good hemocompatibility. Thus, the newly synthesized “Netphob” particle is an interesting candidate for further in vivo studies with the aim to improve the treatment of CKD patients and reduce their high morbidity and mortality risk.