Loop diuretics in anuric hemodialysis patients for the clearance of protein-bound uremic toxins

Abstract

Background: In chronic kidney disease, the accumulation of protein-bound uremic toxins (PBUTs), such as hippuric acid (HA), p-cresyl sulfate (PCS) and indoxyl sulfate (IS), contributes to systemic toxicity and organ dysfunction. These toxins bind to plasma proteins, primarily albumin, rendering them resistant to clearance by conventional dialysis. This study hypothesizes that loop diuretics, particularly torasemide and furosemide, can displace PBUTs from their albumin-binding sites, increasing their free fraction and enhancing their removal during hemodialysis. Methods: This pilot multicenter crossover study included 17 anuric hemodialysis patients recruited from two hospitals. Participants underwent sequential treatment with furosemide and torasemide, each phase separated by a 1-week washout period. Plasma concentrations of HA, PCS and IS were measured pre- and post-dialysis during baseline (no diuretics) and diuretic treatment phases using high-performance liquid chromatography coupled with tandem mass spectrometry. Changes in pre- and post-dialysis toxin levels were evaluated across treatment phases. Repeated measures analysis of variance assessed the effect of each diuretic treatment on toxin levels and clearance rates. Results: Both loop diuretics increased the free fraction and clearance of PBUTs compared with baseline. Torasemide demonstrated higher efficacy in enhancing the clearance of HA (76.8%) compared with furosemide (63.2%) and baseline (57.3%). For PCS, furosemide achieved greater reductions (66.3%) than torasemide (61.8%) and baseline (24%). Indoxyl sulfate clearance increased significantly with both diuretics (59.1% for furosemide and 58.8% for torasemide) compared with baseline (26.2%). Conclusion: This study demonstrates that loop diuretics, especially torasemide, can enhance the clearance of PBUTs during hemodialysis. Their use mobilizes PBUTs from tissue stores and increases their dialyzability. These findings warrant further investigation in larger, long-term studies to validate the efficacy and clinical benefits of this approach.