Abstract
Uremic toxins are a heterogeneous group of molecules that accumulate in the body due to the progression of chronic kidney disease (CKD). These toxins are associated with kidney dysfunction and the development of comorbidities in patients with CKD, being only partially eliminated by dialysis therapies. Importantly, drugs used in clinical treatments may affect the levels of uremic toxins, their tissue disposition, and even their elimination through the interaction of both with proteins such as albumin and cell membrane transporters. In this context, protein-bound uremic toxins (PBUTs) are highlighted for their high affinity for albumin, the most abundant serum protein with multiple binding sites and an ability to interact with drugs. Membrane transporters mediate the cellular influx and efflux of various uremic toxins, which may also compete with drugs as substrates, and both may alter transporter activity or expression. Therefore, this review explores the interaction mechanisms between uremic toxins and albumin, as well as membrane transporters, considering their potential relationship with drugs used in clinical practice.
Highlights
Kidney diseases were the 10th leading cause of death worldwide in 2019, according to the World Health Organization (WHO)
The European Uremic Toxin Work Group (EUTox) reports that uremic toxins can be classified into three groups due to their physicochemical characteristics and their behavior during dialysis [1]: (I) Small-water soluble compounds, such as creatinine and urea; (II) Medium compounds, such as cystatin-C and β2-microglobulin, which can only be removed by large pore size dialysis membranes; and (III) Protein-bound uremic toxins (PBUTs), such as indoles and phenols, which come from dietary amino acid metabolism and are poorly filtered by the dialytic membrane
OCT3 in the choroid plexus is related to the cellular uptake of creatinine and at least partly contributes to the removal of this uremic toxin from the cerebrospinal fluid [134]
Summary
Kidney diseases were the 10th leading cause of death worldwide in 2019, according to the World Health Organization (WHO). It is important to mention fibroblast growth factor 23 (FGF-23), β2-microglobulin, parathyroid hormone (PTH), and pro-inflammatory molecules such as interleukin-6 (IL-6) among the medium compounds [5,6] High levels of these toxins contribute to progressive renal structural damage; they are fundamental to mineral homeostasis maintenance in a healthy organism. The dialytic membrane pores do not effectively remove IS since 90% of it is bound to serum albumin, making the complex too large to be filtered This retention is associated with diverse harmful effects in other organs, such as alterations to thyroid function, endothelial dysfunction, smooth muscle cell proliferation, and atherosclerosis [15,16]. All effects demonstrate that this compound is linked to cardiovascular damage and contributes to the increase in mortality and cardiovascular events in CKD [2,25]
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