Detoxifying Capacity and Kinetics of Prometheus ^® – A New Extracorporeal System for the Treatment of Liver Failure

Abstract

Background/Aims: Extracorporeal liver support therapies have been used for several decades as a bridging therapy prior to liver transplantation or as an addendum to standard medical therapy. The Prometheus^® system represents a cell-free, extracorporeal, liver assist method for the removal of both albumin-bound and water-soluble endogenous toxins. The aim of the present study was to evaluate the removal capacity and selectivity of the different inbuilt dialyzers and adsorption columns during a single 6-hour treatment. Methods: Nine patients with acute on chronic liver failure were included (6 females, age 49 ± 4 years). Levels of endogenous toxins (urea nitrogen [UN, mg/dl], creatinine [Cr, mg/dl], total bilirubin [tB, mg/dl], and bile acids [BA, µmol/l]) and albumin [Alb, g/l] were monitored in blood sampled at different sites (arterial line, venous line and between the absorbers and the high-flux dialyzer) and at various time points (time 0, 30, 60, 120, 240, and 360 min). Results: A significant decrease of the serum level of all toxins was observed (UN 108.7 ± 23.2 vs. 38.1 ± 14.9, Cr 2.4 ± 0.7 vs. 1.2 ± 0.3, tB 31.1 ± 4.1 vs. 17.0 ± 1.6, BA 155.7 ± 32.5 vs. 66.0 ± 15.4; mean ± SEM, time 0 vs. time 360, signed rank rest, all p < 0.005). The reduction rate of UN, Cr, tB and BA amounted to 68.1 ± 5.1, 45.9 ± 6.2, 41.2 ± 5.1, and 58.2 ± 5.0%, respectively. Blood clearances [Cl, ml/min] of all, but especially of the protein-bound toxins declined over time (Cl UN 171.5 ± 4.3 vs. 142.9 ± 16.8; Cl Cr 135.7 ± 10.0 vs. 111.8 ± 9.1; Cl tB 29.3 ± 5.1 vs. 13.7 ± 3.7; Cl BA 84.9 ± 4.8 vs. 45.1 ± 13.3; time 30 vs. time 360; linear mixed models, all p < 0.005). Serum albumin levels decreased by 2.9 ± 0.9 g/l (signed rank test, p = 0.055). Not unexpectedly, tB was almost uniquely cleared by the adsorbers (UN 0.2 ± 1.1, Cr 6.9 ± 5.7, tB 92.3 ± 4.2, BA 62.9 ± 3.9% of total Cl). Conclusion: Both albumin-bound and water-soluble toxins are adequately removed by the Prometheus^® system. Our data suggest that the rate and efficacy of removal of albumin-bound toxins is related to both the strength of the albumin binding and the saturation of the adsorption columns. Limited losses of albumin occur during treatment with the Prometheus system.