Generation, clearance, toxicity, and monitoring possibilities of unaccounted uremic toxins for improved dialysis prescriptions

Abstract

Current dialysis-dosing calculations provide an incomplete assessment of blood purification. They exclude clearances of protein-bound uremic toxins (PB-UTs), such as polyamines, p-cresol sulfate, and indoxyl sulfate, relying solely on the clearance of urea as a surrogate for all molecules accumulating in patients with end-stage renal disease (ESRD). PB-UTs clear differently in dialysis but also during normal renal function. The kidney clears PB toxins via the process of secretion, whereas it clears urea through filtration. Herein, we review the clearance, accumulation, and toxicity of various UTs. We also suggest possible methods for their monitoring toward the ultimate goal of a more comprehensive dialysis prescription. A more inclusive dialysis prescription would retain the kidney-filtration surrogate, urea, and consider at least one PB toxin as a surrogate for UTs cleared through cellular secretion. A more comprehensive assessment of UTs that includes both secretion and filtration is expected to result in a better understanding of ESRD toxicity and consequently, to reduce ESRD mortality.

Correlation between Saliva Levels and Serum Levels of Free Uremic Toxins in Healthy Volunteers

“…These compounds are called “uremic retention solutes” or, when they interact negatively with biological functions, “uremic toxins” (UTs) [ 3 ]. It has recently been suggested that these UTs have a role in the genesis of CKD complications and/or comorbidities, such as endothelial dysfunction, immune dysfunction, aortic calcification, and cardiovascular mortality [ 4 ]. Hence, UT levels must be monitored, to protect patients from disease progression and the corresponding negative outcomes.…”

Renal Biology Driven Macro- and Microscale Design Strategies for Creating an Artificial Proximal Tubule Using Fiber-Based Technologies

“… 2 An important factor responsible for this high mortality is that HD does not include excretion of large lipophilic and protein bound solutes, 3 − 8 leading to the accumulation of large protein-bound uremic toxins ( Figure 1 b), which are associated with an increased risk of cardiovascular disease. 9 − 12 …”

“…Patients who receive HD have a 5 year survival probability below 50%, which is significantly less than patients who received a kidney transplant (>90%) . An important factor responsible for this high mortality is that HD does not include excretion of large lipophilic and protein bound solutes, − leading to the accumulation of large protein-bound uremic toxins (Figure b), which are associated with an increased risk of cardiovascular disease. − …”