Plasma exchange-based plasma recycling dialysis system as a potential platform for artificial liver support

We developed a plasma recycling dialysis (PRD) system based on plasma exchange (PE). In this system, rapid reduction of toxic substances and restitution of deficient essential substances are performed by PE, and subsequent blood purification is performed by dialysis between separated plasma recycled over a purification device and the patient's blood across the membrane of the plasma separator. This study was performed to demonstrate the safety and efficacy of this system. Hyperbilirubinemia was induced by ligating the bile duct in pigs, and 7 days later, only PE for 2 h (group PE) or PE for 2 h followed by PRD for 6 h (group PE + PRD) was performed. The separated plasma was recycled over anion-exchange resin through the extra fiber space of the plasma separator. The safety and efficacy of this system were evaluated based on the values of hemodynamic and laboratory parameters. Transfer from PE to PRD was completed in a few minutes. The hemodynamic status and blood cells counts were stable and hemolysis was not observed during the procedure. In the PE + PRD group, the concentrations of total bile acids continuously decreased (pretreatment, 155.5 +/- 40.6 microM; 2 h [end of PE], 76.1 +/- 14.4 microM; 8 h [end of PRD], 25.8 +/- 9.1 microM) and the value was significantly lower than in the PE group after 6 h. The total bilirubin also continuously decreased during PRD (pretreatment, 55.3 +/- 11.5 microM; 2 h [end of PE], 33.8 +/- 8.4 microM; 8 h [end of PRD], 18.6 +/- 7.7 microM) and was significantly lower than in the PE group after 4 h. No significant change was observed in other laboratory values. This PE-based PRD system allowed a swift transfer from PE to sorbent-based blood purification. The safety of this system was demonstrated and the removal of toxic substances was significant. This study confirmed the clinical utility of this system as a platform for artificial liver support.