Albumin dialysis modeling predicts the impact of polysulfone dialyzers and flow rate on cholic acid and indoxyl sulfate removal

Abstract

Cholic acid (CA) and indoxyl sulfate (IS) are toxins associated with biliary and renal disease. Protein binding prevents removal by traditional dialysis. Dissolving binding molecules such as albumin in dialysate enables detoxification. We created a benchtop albumin dialysis test platform. We used it to validate a mathematical model of CA/IS removal. Toxin-containing blood analog solution was dialyzed using two dialyzers at five flow rates against albumin dialysate. One condition was used to estimate toxin binding affinity to albumin and the free toxin transmembrane transfer coefficient (K_freeA). Other conditions validated modeling results and revealed the impact of dialysate flow rate and dialyzer properties on detoxification (measured by mass spectrometry). We accurately predicted CA/IS removal. The normalized root mean squared error never exceeds 11.5% of the starting amount. Increasing dialysate side flow rate up to 150 mL/min improved toxin removal. Further increases produced no benefit. K_freeA was independent of flow rate. Our data fits a result from the newly developed AMOR system, in which total bile acids declined with treatment. This model and benchtop setup aim to predict clinical CA/IS clearance and optimize device design for clinical trials. This will mean fewer unsuccessful trials and enable testing of new dialysate formulations.