Increase of Octanoate Concentrations During Extracorporeal Albumin Dialysis Treatments

Abstract

Extracorporeal liver support procedures based on albumin dialysis require the use of pharmaceutical-grade human serum albumin (HSA). Those preparations contain octanoate, which is added as stabilizer during the production process. For octanoate, a direct involvement in the pathogenesis of liver failure complications as well as an indirect influence by competitive displacement effects at the albumin molecule have been described. During five Single Pass Albumin Dialysis (SPAD) and three Molecular Adsorbent Recirculating System (MARS) treatments the changes of octanoate concentrations in blood and dialysate were investigated. An octanoate increase in patient blood was observed during passage of the filter for both SPAD (585 micromol/L [338-1022 micromol/L]) (median [range]) and MARS (182 micromol/L [71-437 micromol/L]) during the first three hours of treatment. The molar ratio of octanoate/albumin at the blood outflow was significantly higher during SPAD treatments (1.73 [0.86-2.64] vs. 0.54 [0.31-1.1]; P = 0.001) during MARS. Changes of octanoate blood levels during SPAD were significantly higher than during MARS (P < 0.001). The shift of octanoate from the dialysate to the patient was persistent during SPAD (median 67.6 micromol/min), whereas during MARS a decrease over time was observed (from 25.5 to 7.5 micromol/min). During albumin dialysis procedures a transfer of octanoate into patient blood occurs. The time-course and extent are different between both albumin dialysis procedures. Given the positive clinical effects reported mainly for MARS, the clinical impact of albumin dialysis-associated transfer of octanoate during extracorporeal liver support needs to be evaluated further.

Efficient Removal of Serum Bilirubin by a Novel Artificial Liver Support System Using Albumin Convection: A Pilot Study

“…However, there are some problems including the consumption of large amounts of commercial human albumin, which may lead to unwanted compounds in commercial albumin solution entering the body [15,16] and limited depurative capacity for protein-bound toxins. The intensity of toxins bound to albumin determines their rate to dissociate from albumin, diffuse across membrane, and be removed.…”

Stability of Therapeutic Albumin Solutions Used for Molecular Adsorbent Recirculating System‐Based Liver Dialysis

“…Klammt et al. have recently observed transfer of octanoate to the patient's blood during albumin dialysis (13). In addition, stabilizers will also bind to well‐known binding sites and therefore, potentially interfere with the binding capacity for compounds that need to be cleared from the patient's blood.…”

“… Schematic overview of the MARS according to Klammt et al. (13) 1 = MARS dialysis membrane; 2 = activated charcoal column; 3 = ion‐exchange resin column; 4 = pump; and 5 = low‐flux dialyzer. …”

“…The presence of these stabilizers may result in undesired effects, as Klammt et al. (13) have recently shown that octanoate concentrations in patients undergoing albumin dialysis were significantly increased. In addition, octanoate and N ‐acetyl‐tryptophanate occupy some of the typical albumin binding sites (12,14,15).…”

Industrial stabilizers caprylate and N -acetyltryptophanate reduce the efficacy of albumin in liver patients

“…A test based on the quantification of the binding of an exogenic marker at the benzodiazepine binding site has been established to describe the so‐called albumin‐binding capacity (ABiC) as an indirect measure of the toxin overload of a patient's albumin 7. With progressing liver insufficiency as measured by the Model for End‐Stage Liver Disease score or the Child score, ABiC declines, whereas treatments designed to improve ABiC result in better survival 8…”