MON-125 Release of uremic retention solutes from protein binding by hypertonic predilution hemodiafiltration: a novel therapeutic approach

Abstract

Protein-bound uremic retention solutes accumulate in patients suffering from chronic kidney disease and its removal by hemodialysis is hampered. Therefore, we developed a dialysis technique where the protein-bound uremic retention solutes are removed more efficiently under high ionic strength. Protein-bound uremic solutes such as phenylacetic acid, indoxyl sulfate and p-cresyl sulfate was combined with plasma in the presence of increased ionic strength. The protein integrity of proteins and enzymatic activities were analysed. In-vitro dialysis of albumin solution was performed to investigate the clearance of the bound uremic retention solutes. In-vitro hemodiafiltrations of human blood were performed to investigate the influence of increased ionic strength on blood cell survival. The protein-bound fraction of phenylacetic acid, indoxyl sulfate and p-cresyl sulfate was significantly decreased from 59.4±3.4%, 95.7±0.6%, 96.9±1.5% to 36.4±3.7%, 87.8±0.6% and 90.8±1.3% respectively. The percentage of phenylacetic acid, indoxyl sulfate and p-cresyl sulfate released from protein was 23.0±5.7%, 7.9±1.1% and 6.1±0.2%. The clearance during in-vitro dialysis was increased by 13.1±3.6 %, 68.8±15.1 % and 53.6±10.2 % respectively. There was no difference in NaCl concentrations at the outlet of the dialyser using isotonic and hypertonic solutions In conclusion, this study forms the basis for establishing a novel therapeutic approach to remove the protein-bound retention solutes.