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.

Albumin Dialysis in Artificial Liver Support Systems

“…The two fitted parameters are reasonable according to the literature. 15,23,24 The main forms of the bilirubin purchased were experimentally determined: 94% unconjugated bilirubin and 6% conjugated bilirubin. In simulation, the solution viscosity was assumed the same as the one of water at room temperature.…”

“…Therefore, there is still interest in closed-loop albumin dialysis mode (CLM; the albumin dialysate flows through a closed system, as shown in Figure 1A) for removing protein-bound toxins only by albumin. 5,16,21 Much meaningful theoretical work on the mass transfer model of albumin dialysis and the effect of ultrafiltration on albumin dialysis in OLM has been performed by Patzer et al [13][14][15] However, the detailed comparison between CLM and OLM has not been theoretically reported. Closed-loop albumin dialysis mode is a possible way to help to decrease the use of dialysate (or increase the device portability) and to realize the regeneration and reuse of albumin (or reduce the treatment cost).…”

“…10 Currently, this technology is also extended to the treatment of cholestatic patients with intractable pruritus 11 and the preoperative management of jaundiced patients with hilar cholangiocarcinoma. 12 Albumin dialysis, or bound solute dialysis, [13][14][15] is a detoxifying method in which albumin solution is used as dialysate in a hemodialysis system (Figure 1): the blood containing toxins passes through inside of hollow fibers, whereas the albumin dialysate flows outside hollow fibers counter-currently. In the process, free toxins in blood are transferred to dialysate because of the transmembrane diffusion and convection, bind to albumin in dialysate, and are removed eventually.…”

A Case-Control Study of Single-Pass Albumin Dialysis for Acetaminophen-Induced Acute Liver Failure

“…The water-insoluble proteinbound toxins in the blood are cleared by diffusion and taken up by binding to albumin in the dialysate [11,12] .…”

In vitro Study of Removal of Protein-Bound Toxins

“…A number of artificial liver support systems have been developed to enhance the removal of protein-bound toxins, such as the Prometheus system (Fresenius) [4], the molecular adsorbents-recirculating system (MARS; Gambro) [5], and single-pass albumin dialysis (SPAD), referred to as bound solute dialysis [6]. The orally administered adsorbent AST-120 can also reduce the concentrations of indoxyl sulfate (IS) [7].…”