#1750 Protein-bound uremic toxins removal with post-dilutional hemodiafiltration with high convective volume: a transversal study from hospital clinic Barcelona

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Abstract Background and Aims Protein-bound uremic toxins (PBUTs) are low-molecular-weight uremic toxins which encompass different molecules, with indoxyl sulfate (IS) and p-cresyl sulfate (pCS) being two of the most toxic. Both are related to increased cardiovascular disease and mortality among dialysis patients. The peculiarity of PBUTs is their high affinity for albumin, limiting their clearance by conventional hemodialysis techniques such as high-flux hemodialysis, post-dilutional hemodiafiltration or expanded hemodialysis. Reduction ratio (RR) varies among published studies, but their removal is generally less than 50% for pCS and 55% for IS. Extended dialysis techniques have shown an increase in their removal, up to 59% and 66%, respectively. Our aim was to analyze PBUTs clearance in our hemodialysis unit with post-dilutional hemodiafiltration with high convective volumes (OL-HDF). Method A transversal study was made in the hemodialysis unit of Hospital Clínic of Barcelona during October 2024. Total IS and pCS were measured before and after one OL-HDF session. Total IS and pCS were measured in serum using liquid chromatography-mass spectrometry and post-dialysis levels were corrected for the degree of hemoconcentration and the volume of distribution according to Bergström and Wehle. All sessions were with a Fresenius 5008 or 6008 dialysis monitor. A total of 130 patients were included with a mean age of 71.5 ± 15.9 years (34.6% women). 112 patients (86.3%) realize three-weekly daily sessions with a mean time of 283 ± 23.2 min and blood-flux (Qb) of 423 ± 29.5 mL/min and dialysis-flux (Qd) of 400. The remain 18 patients (13.7%) did nocturnal OL-HDF with a mean time of 423 ± 44.5 min, Qb of 406 ± 29.1 mL/min and Qd of 200. Results Mean IS and pCS RR were 53.9 ± 10.3% and 47.5 ± 12.7% respectively. When these values are divided between groups, RR were 54.1 ± 9.84% for IS and 47 ± 11.7% for pCS in the daily group while 52.2 ± 13.3% for IS and 51 ± 18% for pCS in the nocturnal group (Fig. 1). T-Student analysis for independent groups showed no difference between daily or nocturnal groups (p-value 0.457 and 0.209 for RR of IS and pCS, respectively). Mean convective volumes were 31.8 ± 8.7 with 30 ± 7.2 in the daily-group while 41.7 ± 0.09 in the nocturnal-group. IS and pCS were slightly directly correlated with RR of slow-molecular-weight molecules such as creatinine (r = 0.36 and r = 0.31, respectively) and urea (r = 0.37 and r = 0.25, respectively). In the multiple regression analysis, RR of urea is the only variable statistically significant correlated for IS and pCS (P < 0.001 and p = 0.014, respectively), while convective volume shows a positive tendency with IS and pCS but without significance (p = 0.052 and p = 0.066 respectively). Conclusion Protein-bound uremic toxins are related to cardiovascular morbidity and mortality among patients with chronic hemodialysis treatment. Their removal is one of the facings obstacles in dialysis due to their high affinity to albumin. Our results in PBUTs removal with online-hemodiafiltration are in concordance with the results published in the literature with RR about 55% for IS and 50% for pCS. Their clearance is related to other low-molecular-weight as diffusion is the major responsible. However, all these results, including ours, are insufficient and new strategies for IS and pCS removal are needed. Currently, the use of albumin displacer or adsorptive membranes are promising options under development.

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