Bile acids (BAs) accumulating in the circulation in patients with liver failure are considered to be responsible for pruritus, which strongly impairs quality of life of the affected patients. The aim of this study was the in vitro characterization of different BAs regarding their removability with high-flux dialysis as well as with different adsorbents, and the evaluation of their binding to plasma proteins.
Methods:
Dialysis experiments were conducted in pediatric circuits with human plasma. For the adsorption studies, batch tests using 10% adsorbent in spiked human plasma were carried out. The binding of BAs to plasma compounds was determined by centrifugation of spiked plasma through spin columns. Sieving coefficients were determined using an albumin filter and a high-flux dialyzer.
Results:
With high-flux dialysis, only hydrophilic BAs such as glycocholic and taurocholic acid could be removed efficiently, while all tested BAs were removed by adsorption.
Conclusions:
In conclusion, the hydrophilicity of BAs plays a major role in their removability using extracorporeal approaches. Adsorption-based systems offer particular advantages for the removal of hydrophobic BAs.
RussellDW. The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem. 2003;72:137-174.
2.
AngelinBBjörkhemIEinarssonKEwerthS. Hepatic uptake of bile acids in man. Fasting and postprandial concentrations of individual bile acids in portal venous and systemic blood serum. J Clin Invest. 1982;70(4):724-731.
3.
NealeGLewisBWeaverVPanveliwallaD. Serum bile acids in liver disease. Gut. 1971;12(2):145-152.
4.
CeryakSBouscarelBFrommH. Comparative binding of bile acids to serum lipoproteins and albumin. J Lipid Res. 1993;34(10):1661-1674.
5.
HeubiJESetchellKDBoveKE. Inborn errors of bile acid metabolism. Semin Liver Dis. 2007;27(3):282-294.
6.
SayinSIWahlströmAFelinJet al. Gut microbiota regulates bile acid metabolism by reducing the levels of tauro-beta-muricholic acid, a naturally occurring FXR antagonist. Cell Metab. 2013;17(2):225-235.
7.
RidlonJMKangDJHylemonPBBajajJS. Bile acids and the gut microbiome. Curr Opin Gastroenterol. 2014;30(3):332-338.
8.
YounossiZMKiwiMLBoparaiNPriceLLGuyattG. Cholestatic liver diseases and health-related quality of life. Am J Gastroenterol. 2000;95(2):497-502.
9.
RudmanDKendallFE. Bile acid content of human serum. I. Serum bile acids in patients with hepatic disease. J Clin Invest. 1957;36(4):530-537.
10.
KirbyJHeatonKWBurtonJL. Pruritic effect of bile salts. Br Med J. 1974;4(5946):693-695.
11.
MurphyGMRossABillingBH. Serum bile acids in primary biliary cirrhosis. Gut. 1972;13(3):201-206.
12.
SchaeferBSchaeferFWittmerDEngelmannGWenningDSchmittCP. Molecular Adsorbents Recirculating System dialysis in children with cholestatic pruritus. Pediatr Nephrol. 2012;27(5):829-834.
13.
BellmannRGraziadeiIWFeistritzerCet al. Treatment of refractory cholestatic pruritus after liver transplantation with albumin dialysis. Liver Transpl. 2004;10(1):107-114.
14.
ParésAHerreraMAvilésJSanzMMasA. Treatment of resistant pruritus from cholestasis with albumin dialysis: combined analysis of patients from three centers. J Hepatol. 2010;53(2):307-312.
15.
KrisperPStauberRE. Technology insight: artificial extracorporeal liver supporthow does Prometheus compare with MARS?Nat Clin Pract Nephrol. 2007;3(5):267-276.
16.
StauberREKrisperP. Mars and prometheus in acute-on-chronic liver failure: Toxin elimination and outcome. Transplantationsmedizin. 2010;22:333-338.
17.
RifaiKHaferCRosenauJet al. Treatment of severe refractory pruritus with fractionated plasma separation and adsorption (Prometheus). Scand J Gastroenterol. 2006;41(10):1212-1217.
18.
RodaACappelleriGAldiniRRodaEBarbaraL. Quantitative aspects of the interaction of bile acids with human serum albumin. J Lipid Res. 1982;23(3):490-495.
19.
MalavoltiMFrommHCeryakSShehanKL. Interaction of potentially toxic bile acids with human plasma proteins: binding of lithocholic (3 alpha-hydroxy-5 beta-cholan-24-oic) acid to lipoproteins and albumin. Lipids. 1989;24(7):673-676.
20.
AucellaFVigilanteMGesueteA. Review: the effect of polymethylmethacrylate dialysis membranes on uraemic pruritus. NDT Plus. 2010;3(Suppl 1):i8-i11.
21.
SalvioliGLugliRPradelliJMGigliottiG. Bile acid binding in plasma: the importance of lipoproteins. FEBS Lett. 1985;187(2):272-276.
22.
HarmSFalkenhagenDHartmannJ. Pore sizea key property for selective toxin removal in blood purification. Int J Artif Organs. 2014;37(9):668-678.
StampDJenkinsG. An overview of bile-acid synthesis, chemistry and function. In: JenkinsGHardieLJ eds. Bile acids: Toxicology and bioactivity. Cambridge: RSC Publishing. 2008;1-13.
25.
AldiniRRodaALabateAMCappelleriGRodaEBarbaraL. Hepatic bile acid uptake: effect of conjugation, hydroxyl and keto groups, and albumin binding. J Lipid Res. 1982;23(8):1167-1173.
26.
HofmannAF. Bile acids: The good, the bad, and the ugly. News Physiol Sci. 1999;14:24-29.
27.
SzepietowskiJCSikoraMKusztalMSalomonJMagottMSzepietowskiT. Uremic pruritus: a clinical study of maintenance hemodialysis patients. J Dermatol. 2002;29(10):621-627.
28.
SzepietowskiJC. Selected elements of the pathogenesis of pruritus in haemodialysis patients. Med Sci Monit. 1996;2(3):HY343-347.
29.
KatoAHamadaMMaruyamaTMaruyamaYHishidaA. Pruritus and hydration state of stratum corneum in hemodialysis patients. Am J Nephrol. 2000;20(6):437-442.
30.
DimkovićNDjukanovićLRadmilovićABojićPJuloskiT. Uremic pruritus and skin mast cells. Nephron. 1992;61(1):5-9.
31.
EisendleKMüllerHOrtnerEet al. Pruritus of unknown origin and elevated total serum bile acid levels in patients without clinically apparent liver disease. J Gastroenterol Hepatol. 2011;26(4):716-721.
