Comparing Ibuprofen and Loop Diuretics for Protein-Bound Uremic Toxins Clearance During Hemodialysis

Protein-bound uremic toxins (PBUTs), such as indoxyl sulphate (IS) and p-cresyl sulphate (pCS) are associated with cardiovascular mortality in patients undergoing hemodialysis. Because of their high albumin affinity, conventional dialysis techniques achieve poor clearance. This study aims to evaluate the efficacy of different competitive binding displacement strategies using ibuprofen and loop diuretics during online hemodiafiltration (OL-HDF).

A longitudinal, cross-over study in 12 patients undergoing chronic hemodialysis was performed. Each patient underwent 6 different dialysis modalities based on postdilutional HDF. The experimental arms included the following: (i) Standard postdilutional HDF (control), (ii) High-flux hemodialysis (HF-HD) (iii) Oral furosemide 1h predialysis, (iv) Oral torasemide 1h predialysis, (v) 1h arterial infusion of furosemide, and (vi) 1h arterial infusion of ibuprofen. Reduction ratios (RR) for IS and pCS were calculated for each session. Statistical analysis was performed using 1-way repeated measures analysis of variance with Bonferroni post hoc correction.

Arterial administration of ibuprofen was the only strategy that significantly enhanced PBUT removal, achieving mean RR of 65% for IS and 60% for pCS (P < 0.05 vs. baseline OL-HDF). In contrast, neither oral nor arterial administration of loop diuretics showed a statistically significant increase in the RR of IS or pCS when compared with OL-HDF. No acute adverse events were reported during the pharmacological interventions.

Prefilter arterial infusion of ibuprofen is the most effective strategy for increasing the intradialytic clearance of IS and pCS during OL-HDF. The lack of efficacy observed with furosemide suggests a ceiling effect in high-volume HDF, where only high-affinity competitors can further displace PBUTs from albumin-binding sites. Pharmacological displacement represents a promising adjunct to convective therapies to optimize protein-bound uremic toxin removal.