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.