The Interplay between Uremic Toxins and Albumin, Membrane Transporters and Drug Interaction

Author(s)

da Cunha, Regiane Stafim ; Bueno Azevedo, Carolina Amaral ; Falconi, Carlos Alexandre ; Ruiz, Fernanda Fogaca ; Liabeuf, Sophie ; Carneiro-Ramos, Marcela Sorelli ; Marques Stinghen, Andrea Emilia

• Document type: Journal article
• Source: TOXINS; v. 14, n. 3, p. 24-pg., 2022-03-01.

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. (AU)

• FAPESP's process: 19/11077-0 - Cardiac alterations induced by renal inflammation models: participation of the Klotho/FGF-23 axis
• Grantee: Marcela Sorelli Carneiro Ramos
• Support Opportunities: Regular Research Grants