Challenges of reducing protein-bound uremic toxin levels in chronic kidney disease and end stage renal disease.

The prevalence of chronic kidney disease (CKD) in the worldwide population is currently estimated between 11% and 13%. Adequate renal clearance is compromised in these patients and the accumulation of a large number of uremic retention solutes results in an irreversible worsening of renal function which can lead to end stage renal disease (ESRD). Approximately three million ESRD patients currently receive renal replacement therapies (RRTs), such as hemodialysis, which only partially restore kidney function, as they are only efficient in removing mainly small, unbound solutes from the circulation while leaving larger and protein-bound uremic toxins (PBUTs) untouched. The accumulation of PBUTs in patients highly increases the risk of cardiovascular events and is associated with higher mortality and morbidity in CKD and ESRD. In this review, we address several strategies currently being explored toward reducing PBUT concentrations, including clinical and medical approaches, therapeutic techniques, and recent developments in RRT technology. These include preservation of renal function, limitation of colon derived PBUTs, oral sorbents, adsorbent RRT technology, and use of albumin displacers. Despite the promising results of the different approaches to promote enhanced removal of a small percentage of the more than 30 identified PBUTs, on their own, none of them provide a treatment with the required efficiency, safety and cost-effectiveness to prevent CKD-related complications and decrease mortality and morbidity in ESRD.
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