Uremic Toxins: Removal with Different Therapies

Abstract

A convenient way to classify uremic solutes is to subdivide them according to the physicochemical characteristics influencing their dialytic removal into small water-soluble compounds (<500 Da), protein-bound compounds, and middle molecules (>500 Da). The prototype of small water-soluble solutes remains urea although the proof of its toxicity is scanty. Only a few other water-soluble compounds exert toxicity (e.g., the guanidines, the purines), but most of these are characterized by an intra-dialytic behavior, which is different from that of urea. In addition, the protein-bound compounds and the middle molecules behave in a different way from urea, due to their protein binding and their molecular weights, respectively. Because of these specific removal patterns, it is suggested that new approaches of influencing uremic solute concentration should be explored, such as specific adsorptive systems, alternative dialytic timeframes, removal by intestinal adsorption, modification of toxin, or general metabolism by drug administration. Middle molecule removal has been improved by the introduction of large pore, high-flux membranes, but this approach seems to have come close to its maximal removal capacity, whereas multicompartmental behavior might become an additional factor hampering attempts to decrease toxin concentration. Hence, further enhancement of uremic toxin removal should be pursued by the introduction of alternative concepts of elimination.

Treatment Time and Ultrafiltration Rate Are More Important in Dialysis Prescription than Small Molecule Clearance

“…Removal of MMs (including phosphorus) is only slightly dependent on blood and dialysate flows [13] , so compensating shortened dialysis time by increasing blood flow is not effective. This is not only related to the slow diffusion of these molecules through the membrane, but also to multicompartmental behavior, i.e., slow diffusion from the extravascular space to the plasma [78] . This process may be compared to the poor 'plasma-refilling rate' of water and sodium in high ultrafiltration rate hemodialysis.…”

A need for a paradigm shift in focus: From Kt/Vurea to appropriate removal of sodium (the ignored uremic toxin)

“…Removal of MMs (including phosphorus) is only slightly dependent on blood and dialysate flows, so compensating shortened dialysis time by increasing blood flow is not effective. This is not only related to the slow diffusion of these molecules through the membrane, but also to multicompartmental behavior, that is, slow diffusion from the extravascular space to the plasma . This process may be compared to the poor “plasma‐refilling rate” of water and sodium in high ultrafiltration rate hemodialysis.…”

“…This is not only related to the slow diffusion of these molecules through the membrane, but also to multicompartmental behavior, that is, slow diffusion from the extravascular space to the plasma. 136 This process may be compared to the poor "plasma-refilling rate" of water and sodium in high ultrafiltration rate hemodialysis. It is worth realizing that even for removal of small molecules, an increased time of dialysis is more effective than increased blood and dialysate flows, because spKt/V urea (single pool) is directly proportional to dialysis time, but K is exponentially, not linearly, proportional to blood and dialysate flows.…”

Fallacies of High‐Speed Hemodialysis

“…This is not only related to the slow diffusion of these molecules through the membrane, but also to multicompartmental behavior, i.e., slow diffusion from the extravascular space to the plasma [67]. Removal of middle molecules (including phosphorus) is only slightly dependent on blood and dialysate flows, so compensating shortened dialysis time by increasing blood flow is not effective.…”

“…Removal of middle molecules (including phosphorus) is only slightly dependent on blood and dialysate flows, so compensating shortened dialysis time by increasing blood flow is not effective. This is not only related to the slow diffusion of these molecules through the membrane, but also to multicompartmental behavior, i.e., slow diffusion from the extravascular space to the plasma [67]. This process may be compared to the poor ''plasma refilling rate'' of water and sodium in high-speed hemodialysis.…”