Middle-Molecule Uremic Toxin Removal via Hemodialysis Augmented with an Immunosorbent Packed Bed

Abstract

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.

Feasibility Assessment of Parathyroid Hormone Adsorption by Using Polysaccharide-Based Multilayer Film Systems

“…However, PTH is a middle-sized uremic toxin and cannot be removed with conventional dialysis [ 6 , 7 ]. Not only do the traditional dialysis membranes not remove the PTH and other middle- sized toxins, the concentration of PTH tends to accumulate in the body during standard dialysis due to the hemoconcentration effect [ 8 ]. Therefore, specific and optimized design for PTH removal is necessary for CKD patients, especially for the patients with hyperparathyroidism disease [ 9 ].…”

High performance thin-film nanofibrous composite hemodialysis membranes with efficient middle-molecule uremic toxin removal

“…Although the hemodialysis has certainly changed the prognosis of chronic/acute kidney disease, the mortality rates of the patients with renal diseases remain unacceptably high (exceeding 20%) [6]. The substantial shortcoming, which the hemodialysis membranes are inadequate to remove middle-molecules, results in the disappointing outcomes for hemodialysis patients [7].…”

Innovative strategy with potential to increase hemodialysis efficiency and safety

“…In the literature1718, Ag NP-treated catheters have been prepared for use in HD to prevent bacterial adhesion and to act as antibacterial coatings. Xia et al 19,. established in vitro that elevated levels of parathyroid hormone can be reduced to normal levels within a typical dialysis session by using an immunosorptive packed bed in conjunction with HD.…”

“…Xia et al . 19 , established in vitro that elevated levels of parathyroid hormone can be reduced to normal levels within a typical dialysis session by using an immunosorptive packed bed in conjunction with HD. As reported 20 , reducing the dialysate sodium level can lower blood pressure for older patients and women.…”