Principles of Bound Solute Dialysis

Abstract

Toxins that bind to albumin in the bloodstream and are associated with progressing liver failure have proven refractory to removal by conventional hemodialysis. Such toxins can, however, be removed by adding a binder to the dialysate that serves to capture the toxin as it is dialyzed across the membrane. Several approaches based upon this concept are in various stages of clinical evaluation. The thermodynamic basis common to these approaches has been used to develop an engineering description of 'bound solute dialysis' which has further been used to define the clinical expectations and limitations of the approach. Three dimensionless, independently controllable, operating parameters emerged from this analysis (i): kappa, the dialyzer mass transfer/blood flow rate ratio (clinical range: 0.5-2.5); (ii) alpha, the dialysate/blood flow rate ratio (clinical range: 0.1-2.0); and (iii) beta, the dialysate/blood binder concentration ratio (clinical range: 0.02-5.0). In the absence of binder in the dialysate, bound toxin removal is sensitive to kappa and alpha, with greater removal associated with greater kappa and/or alpha. Bound toxin removal, however, is dependent primarily upon kappa and independent of alpha and beta once a small amount of binder, beta > 0.02, is added to the dialysate. The improvement in bound toxin removal over conventional hemodialysis is dependent upon how tightly the toxin binds albumin ranging from a 6-fold increase for a relatively tightly bound solute such as unconjugated bilirubin, to 1.5-fold increase for a less tightly bound drug such as warfarin at 24 h perfusion time. Clinically, bound solute dialysis can be practiced in single-pass mode with as little as 1-2 g albumin/L dialysate. Because of the constraints imposed by the thermodynamic nature of the process, intervention should be made as early in the disease progression as feasible.