Albumin Binding Capacity (ABiC) is reduced in commercially available Human Serum Albumin preparations with stabilizers

Introduction

Albumin is clinically used as a liver function test describing the metabolic liver capacity and so as a marker of severity of illness in multiple scoring systems. Reduction of serum albumin concentration is correlated with an increased mortality in different diseases, therefore albumin concentration is seen and used as an independent predictor of severity of illness in different clinical scoring systems [1] [2] [3]. However, estimation of albumin concentration does not provide information about the existing functional status or capacity to transport endogenous substances (e. g. prostaglandin, bilirubin, bile acids, fatty acids, thyroid hormones, endogenous steroids and benzodiazepines) or drugs (e. g. diuretics, ß-Lactam-antibiotics, sedatives). Most of the albumin ligands are bound to one of the two common binding sites I or II, as described by Sudlow and colleagues [4; 5]. Free fatty acids, metal ions like Copper and bilirubin are bound selectively to specific binding domains [6] [7] [8] [9] [10] [11].

Especially in acute liver failure or in end stage liver disease (ESLD) the impaired excretory capacity for lipophilic substances leads to an accumulation of these mostly albumin bound or transported compounds. According to the reduced albumin concentration and the limited transport capacity substances with a less affinity will be competitive displaced by ligands with a higher binding affinity to albumin. Metabolic pathways can be affected by the so increased unbound fraction of various substances which can results in worsening of hepatic failure or impaired pharmacokinetic or toxic effects of drugs. Impaired binding properties in diseases with an accumulation of albumin bound substances are described for single substances bound to one of the two major binding sites I or II.

For bilirubin, bound selectively to a specific bilirubin binding site, a equilibrium dialysis based test system has been developed to evaluate the remaining transport capacity of albumin in hyperbilirubinaemia [12] [13] [14].

Hypoalbuminaemia can be corrected by intravenous infusion of albumin containing products like Fresh Frozen Plasma (FFP), serum preparation or normal serum albumin. In the commercially available 5 %, 20 % or 25 % albumin solutions either caprylate (octanoate) or N-acetyl-tryptophanate (N-AT) are added to a molar ratio of 5:1 per mol albumin. This is necessary to avoid polymerization during pasteurization (60 °C for 10h). However, the used stabilizers are bound to albumin binding site II and therefor the transport function of pasteurized albumin is impaired and after intravenous infusion endogenous albumin ligands may be displaced [15] [16] [17].

Considering the need of a simply estimation of existing albumin transport function especially in liver disease a new laboratory test has been developed which enables the binding site specific characterization of the Albumin Binding Capacity (ABiC). Measuring either the bound (direct test) or the unbound (indirect test) fraction of a site specific marker and comparison with a reference the available transport capacity can be expressed quantitatively.

Based on the hypothesis, that an accumulation of albumin bound substances in excretory liver failure as well as the stabilizers present in commercially available albumin preparations may reduce the available binding and therefor transport capacity of albumin, ABiC was measured in different albumin preparations with or without stabilizers, in healthy volunteers and in patients with severe liver failure.

References

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