Middle-molecule uremic toxin removal via hemodialysis augmented with an immunosorbent packed bed

Outcomes for hemodialysis patients are disappointing. Middle molecules too large to cross dialysis membranes, such as parathyroid hormone (PTH), accumulate in the blood and are implicated in a complex collection of symptoms known as the uremic syndrome. We report our investigation into the removal of middle molecules by adding an immunosorptive packed bed, known as a hemoperfuser, to hemodialysis. We established in vitro that PTH can be reduced to normal levels within a typical dialysis session. We then developed a mathematical model of a combined hemodialysis-hemoperfusion system integrated with a patient pharmacokinetics model. We validated the model in vitro and then scaled up it up to clinical practice. We predict that immunosorptive hemoperfusion can reduce PTH levels to the normal range within the clinical scenario as well. However, we also predict that, because of the high synthesis rate of PTH in vivo, the toxin concentration might recover so rapidly as to limit the effectiveness of added immunosorption.