#2931 Advancing personalized extracorporeal therapies for albumin bound toxins through serum albumin binding function

Abstract

Abstract Background and Aims Liver failure poses a significant clinical challenge with compromised functionality of the liver and accumulation of toxic metabolites. The lack of bedside-compatible methods to evaluate treatment response during therapy underscores the urgent need for refined diagnostic tools. Albumin, the principal transport protein, reflecting the elevated toxin and metabolite levels in liver failure, assumes a critical role in assessing the severity of hepatic dysfunction. This research introduces a novel method centered on a dansylsarcosine-based kinetic modeling of serum albumin binding, aiming to improve therapeutic decision-making in hepatic failure. This biomarker is designed to offer critical insights into albumin's dynamic interactions, essential for assessing liver function and effectiveness of therapeutic interventions. The study aims to supplement existing diagnostic methods, providing a more comprehensive evaluation of irreversible damages of albumin in liver failure and guiding more effective treatment strategies. Method In this study, we employed a novel method for measuring binding affinity at varying levels of dansylsarcosine, aiming to describe the kinetic properties of the Sudlow II binding site. The binding behavior of albumin under various concentrations of dansylsarcosine was characterized using a modified Michaelis-Menten kinetic model. To enhance accuracy, a formula correction was employed for both intrinsic absorbance and the influence of dansylsarcosine. The method facilitates kinetic modeling, exploring the behavior of the binding site under diverse ligand concentrations. Emerging from this are two key players: Bmax and Kd. Bmax quantifies the maximum capacity of binding sites available for occupation by dansylsarcosine. Kd signifies the concentration of dansylsarcosine at which half of the Sudlow II binding sites are saturated. The method was applied to a patient database of patients with hepatic failure treated with OPAL or MARS liver support systems (albumin dialysis with albumin regeneration). The applied analysis focused on the correlation with existing clinical scores and the description of therapeutic effects. Results The new method correlates with established markers, scores and therapeutic effects. For Patient samples from the OPALESCE database, Bmax and Kd exhibited correlations with established albumin biomarkers. Subgroup analysis revealed associations with clinical scores such as GCS, SOFA, MELD, ACLF, CLIF-OF and ABiC emphasizing the clinical relevance of Bmax and Kd values. Therapeutic effects were assessed using the OPALESCE database, demonstrating the capability of Bmax and Kd to describe therapy outcomes. Significant differences between the start and end of the first treatment were detected for MARS with Bmax and OPAL with Kd. Bmax and Kd values proved to be valuable indicators for therapeutic effects, aligning with established parameters such as ABiC and the CLIF-OF Score. These findings underscore the potential clinical utility of Bmax and Kd as robust markers for assessing therapy outcomes in liver support interventions. Conclusion The results help to provide a comprehensive understanding of albumin binding dynamics in patients with hepatic failure, offering a valuable tool for therapeutic decisions. The impact of therapy can be described using Bmax and Kd, both of which correlate with established clinical scores within the patient population. Bmax unveils irreversible damages to the albumin molecule, showcasing its potential to identify scenarios where applied therapies fail to enhance albumin binding functions. This insight prompts the consideration of alternative therapeutic pathways, including the consideration of therapeutic plasma exchange when extracorporeal methods are insufficient, showcasing the biomarker's utility in guiding precision therapeutic decisions for improved outcomes in hepatic failure management. The significance of albumin function for uraemic toxins needs to be further investigated. Optimization of dialysis for patients with renal insufficiency appears possible.