Uremic toxins

 

Uremic toxins

 

Uremic syndrome is a complex mixture of clinical changes that can be attributed to one or more of variable solutes retained in uremia/CKD. Database concerned with the nature & kinetic behavior of these compounds may be beneficial with the advent of a de novo therapeutic agent introduced in the future. A constellation of factors that have frequently been omitted, may interfere with the uremic solute levels and their effect on physiological functions:

1)    Traditional sources of uremic solutes ma include dietary protein metabolism, additional sources e.g. environmental contamination, food additives, traditional stimulants (coffee, tea), herbal medications, or addiction to psychedelic agents may have their roles in uremic toxicity.

2)    A variety of solutes have a toxic capacity to invade the body via the intestinal root. Alterations in the composition of intestinal microbiota or changes in intestinal production, absorptive capacity, transfer, and metabolism may interfere with serum levels of these toxins.

3)    Certain uremic solutes can interfere with the functions that directly impact the biochemical action of other substances (e.g., the expression of parathyroid hormonal [PTH] receptors, the response to 1, 25 (OH)2 vit. D3, in addition to the protein binding and breakdown of many other solutes).

4)    Most ptns with RF use multiple drugs. Interaction of these agents with protein binding and/or tubular clearance of uremic solutes may impact their biological effect their biological effect.

5)    Lipophilic components may be responsible at least partially on functional alterations of uremia; these are inadequately cleared by current DX programs.

6)    The major strategy on current use to limit the uremic solute levels is dialysis. However, DX is NOT specific and can also remove the essential components.

7)    Uremic solutes accumulation occurs not only in the plasma but also intracellular, where biological activity is mostly in action. Removal of intracellular components during DX through the cell membrane may be impeded, leading to many compartmental kinetics & impaired detoxification, unless DX duration and/or frequency have been augmented.

 

Biochemical changes can be triggered by a broad spectrum of components:

1)    Some: small & water soluble (e.g., urea, guanidines, phosphate, oxalate).

2)    Some: lipophilic and/or protein bound (e.g., p-cresyl sulfate, homocysteine, indoles).

3)    Some: larger with a middle-molecule range (e.g., beta2-microglobulin, PTH).

4)    Some components of one group can affect generation/behavior of other comp-onents from another one (e.g., guanidines can increase generation of TNFa).

Optimal clearance for each type of molecule may be obtained with a different type of extracorporeal therapy (e.g., via large-pore membranes and/or dialyzers or devices with a high adsorptive capacity for some or several of the uremic toxins). Adsorption with DX devices currently available is of little importance. More specific devices with large surface areas must be developed before adequate adsorption can be obtained

 

Solute levels is also controlled by intestinal intake & preserved kidney function:

1)    Intestinal uptake can be decreased by dietary uptake control, via oral sorbents, or via intestinal flora control by adding of prebiotics or probiotics.

2)    Preserving residual kidney function may also crucial to guarantee more removal of retention solutes.

3)    Therapeutic maneuvers by adding drugs countering biological effect of uremic solutes.

 

Lastly, choosing marker molecules for retained uremic toxins & dialytic removal should be reevaluated. It has been increasingly clear that the current markers, which are all small, water-soluble compounds (urea, creatinine), are NOT always representing their kinetic behavior for middle molecules, lipophilic/protein-bound components, and even other hydrosoluble components. Nevertheless, it may be realistic to admit another marker that is representing ALL solutes or that are responsible for the manifestation of uremic syndrome.