title: Binding of bilirubin and bromosulphthalein to albumin: implications for understanding the pathophysiology of liver failure and its management.
abstract: The binding/transporting functions of albumin provide the rationale for using albumin dialysis (e.g., molecular adsorbents recirculating system [MARS]) in liver failure. This study investigates these properties in vitro, validating the findings in vivo. In vitro bromosulphthalein (BSP) and bilirubin-spiked plasma were dialyzed against albumin and sampled. In vivo serum biochemistry was analyzed in: 7 MARS-treated liver failure patients; 98 MARS-treated patients from the MARS Registry; and 8 patients receiving albumin infusion. In vitro BSP concentrations did not equilibrate, but the molar ratio of BSP to albumin (C(BSP)/C(alb)) did, with no subsequent transmembrane transport, suggesting that the C(BSP)/C(alb) gradient (rather than simple diffusion) drives BSP transport. Bilirubin was transported similarly. In vivo serum bilirubin reduction during MARS sessions (n = 26) correlated with pre-treatment bilirubin (r = 0.42), but better (r = 0.85) with pre-treatment molar ratio of bilirubin to albumin (C(bilirubin)/C(alb)). The strongest correlation was between C(bilirubin)/C(alb) reduction and pre-treatment C(bilirubin)/C(alb) (r = 0.9). A similar pattern was observed in the MARS Registry patients. After albumin infusion (n = 8), both serum albumin and bilirubin increased, while C(bilirubin)/C(alb) remained unchanged. C(bilirubin)/C(alb) appears to be important in albumin dialysis, and generally in liver disease patients, reinforcing the importance of the toxin-binding functions of albumin in liver disease.
authors.affiliation: Institute of Hepatology, University College London, London, UK.
authors.forename: Christian
authors.initials: C
authors.lastname: Steiner
authors.forename: Sambit
authors.initials: S
authors.lastname: Sen
authors.forename: Jan
authors.initials: J
authors.lastname: Stange
authors.forename: Roger
authors.initials: R
authors.lastname: Williams
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
mesh_terms: D000327:Adsorption; D000418:Albumins / Q000008:administration & dosage / Q000378:metabolism*; D001663:Bilirubin / Q000097:blood / Q000378:metabolism*; D001692:Biological Transport; D004396:Coloring Agents / Q000378:metabolism*; D003956:Dialysis; D006801:Humans; D007275:Injections, Intravenous; D017093:Liver Failure / Q000378:metabolism* / Q000503:physiopathology / Q000628:therapy; D008567:Membranes, Artificial; D012042:Registries; D012709:Serum Albumin / Q000378:metabolism; D013448:Sulfobromophthalein / Q000378:metabolism*
chemical_list: D000418:Albumins; D004396:Coloring Agents; D008567:Membranes, Artificial; D012709:Serum Albumin; D013448:Sulfobromophthalein; D001663:Bilirubin