Kidney clearances of protein-bound uremic toxins predict outcomes in chronic kidney disease: a prospective cohort study

Abstract

This prospective cohort study investigated the kidney clearance of protein-bound uremic toxins (PBUTs)—specifically, indole sulfate (IS), p-cresol sulfate (pCS), and indole-3-acetic acid (IAA)—across various stages of chronic kidney disease (CKD) stages and their associations with adverse clinical outcomes. From July 2018 to December 2020, 186 non-dialysis CKD patients were enrolled and followed until June 2025. Serum and 24-hour (24 h) urine PBUT levels were measured, and kidney clearances were analyzed. The findings indicated a decrease in the 24 h kidney clearances of IS (Cis), pCS (Cpcs), and IAA (Ciaa) corresponding with a reduction in glomerular filtration rate (GFR) across the CKD stages. For instance, the clearance of indoxyl sulfate was observed to decline from 26.7 mL/min in stage 1 to 2.2 mL/min in stage 5. PBUT clearances and fractional clearances were generally unaffected by 24 h urinary protein levels, with the exception of fractional clearance of IAA. Elevated levels of Cis and Ciaa were independently correlated with decreased risks of renal outcomes (IS: HR 0.964; IAA: HR 0.941) and hospitalization (IS: HR 0.984; IAA: HR 0.961). The study concluded that the 24 h kidney clearances of IS and IAA are independently associated with renal adverse outcomes and hospitalization, with minimal influence from urinary protein excretion.