We do not know the full cascade of metabolic changes that occur in a person when kidneys fail. However, we observe multisystem progressive deterioration as kidney function declines. Once endstage kidney disease has developed, transplantation offers the best outcome but at the expense of immunosuppression. Currently, the scarcity of replacement organs mandates that depuration occur by means of dialytic therapy, which typically involves extracorporeal cleansing with dialysate during hemodialysis. In this procedure, blood and dialysate are separated by a semipermeable porous membrane through which water and solutes pass, limited by the water-permeability characteristics and pore widths of the membrane. Molecules and ions of a given molecular cutoff (as calculated by weight plus charge plus steric hindrance), almost to the size of albumin, may conceivably transit through the pores. The original commercially available cellulose-based hemodialysis membranes were thick and strong with a molecular weight cutoff of approximately 1000 Daltons. The development of biocompatible, synthetic, high-flux membranes allowed for greater water permeability with wider pores. Solute is removed by means of concentration gradient-driven diffusion from blood (plasma water) to dialysate but also convectively by means of solvent drag, in which solute that is dissolved in plasma water traverses the dialysis membrane, driven by the hydraulic pressure of flowing blood (positive) and dialysate (negative) as pumped through the system.
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