Finalist: Displacer-Enhanced Hemodialysis: Improving The Intradialytic Removal Of Protein-Bound Uremic Toxins Using Binding Competitors

Hemodialysis is a life-sustaining treatment for the almost half a million patients who have lost their kidney function and are currently receiving chronic hemodialysis in the United States. Hemodialysis can remove uremic toxins (deleterious substances that accumulate in the body as kidney function declines). One class of toxins, however, is notoriously difficult to remove by hemodialysis: protein-bound uremic toxins. This is because, in the patient's blood, these toxins are bound to a protein called albumin. Albumin itself is too large to be removed with conventional hemodialysis, and since it clings to these toxins, they cannot be effectively removed. Research suggests that these toxins negatively affect our patients' health, and yet no practical progress has been made in recent decades to more effectively remove these toxins from the blood.

We have developed a concept called "displacer-enhanced dialysis": during the dialysis treatment, a displacer substance is infused into the dialysis machine's blood tubing upstream of the artificial kidney. This displacer binds to the same binding sites on albumin as the toxins. Thus, it quite effectively competes with the toxins for their albumin binding, displaces them from the albumin molecule, and, once they are free, they can then be easily removed in the artificial kidney. All of this happens outside of the patient's body.

In laboratory experiments, we have seen up to a 3-fold increase in the removal rate of these toxins. Recently, a study in human dialysis patients has confirmed this effect. But the displacers used so far for these proof-of-concept studies are not suitable for long-term use in patients.

The goals of this KidneyX proposal are: 1. To advance our search for an ideal displacer (or a combination of displacers) that can be used routinely in chronic hemodialysis, and 2. To study the effects of longer-term use of such displacers.

Submitted by Peter Kotanko, Xia Tao, Stephan Thijssen, Vaibhav Maheshwari, and Nadja Grobe on behalf of Renal Research Institute LLC.

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