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A Novel Strategy for Enhanced Sequestration of Protein-Bound Uremic Toxins Using Smart Hybrid Membranes.

ABSTRACT: Currently available hemodialysis (HD) membranes are unable to safely remove protein-bound uremic toxins (PBUTs), especially those bonded to human serum albumin (HSA). To overcome this issue, the prior administration of high doses of HSA competitive binders, such as ibuprofen (IBF), has been proposed as a complementary clinical protocol to increase HD efficiency. In this work, we designed and prepared novel hybrid membranes conjugated with IBF, thus avoiding its administration to end-stage renal disease (ESRD) patients. Two novel silicon precursors containing IBF were synthesized and, by the combination of a sol-gel reaction and the phase inversion technique, four monophasic hybrid integral asymmetric cellulose acetate/silica/IBF membranes in which silicon precursors are covalently bonded to the cellulose acetate polymer were produced. To prove IBF incorporation, methyl red dye was used as a model, thus allowing simple visual color control of the membrane fabrication and stability. These smart membranes may display a competitive behavior towards HSA, allowing the local displacement of PBUTs in future hemodialyzers.

SUBMITTER: Lopes M

PROVIDER: S-EPMC10059720 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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A Novel Strategy for Enhanced Sequestration of Protein-Bound Uremic Toxins Using Smart Hybrid Membranes.

Lopes Madalena M Pires Rita F RF Faria Mónica M Bonifácio Vasco D B VDB

Journal of functional biomaterials 20230228 3

Currently available hemodialysis (HD) membranes are unable to safely remove protein-bound uremic toxins (PBUTs), especially those bonded to human serum albumin (HSA). To overcome this issue, the prior administration of high doses of HSA competitive binders, such as ibuprofen (IBF), has been proposed as a complementary clinical protocol to increase HD efficiency. In this work, we designed and prepared novel hybrid membranes conjugated with IBF, thus avoiding its administration to end-stage renal ...[more]

PMID: 36976062

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Project description:Background and objectivesCurrent hemodialysis techniques fail to efficiently remove the protein-bound uremic toxins p-cresyl sulfate and indoxyl sulfate due to their high degree of albumin binding. Ibuprofen, which shares the same primary albumin binding site with p-cresyl sulfate and indoxyl sulfate, can be infused during hemodialysis to displace these toxins, thereby augmenting their removal.Design, setting, participants, & measurementsWe infused 800 mg ibuprofen into the arterial bloodline between minutes 21 and 40 of a conventional 4-hour high-flux hemodialysis treatment. We measured arterial, venous, and dialysate outlet concentrations of indoxyl sulfate, p-cresyl sulfate, tryptophan, ibuprofen, urea, and creatinine before, during, and after the ibuprofen infusion. We report clearances of p-cresyl sulfate and indoxyl sulfate before and during ibuprofen infusion and dialysate concentrations of protein-bound uremic toxins normalized to each patient's average preinfusion concentrations.ResultsWe studied 18 patients on maintenance hemodialysis: age 36±11 years old, ten women, and mean vintage of 37±37 months. Compared with during the preinfusion period, the median (interquartile range) clearances of indoxyl sulfate and p-cresyl sulfate increased during ibuprofen infusion from 6.0 (6.5) to 20.2 (27.1) ml/min and from 4.4 (6.7) to 14.9 (27.1) ml/min (each P<0.001), respectively. Relative median (interquartile range) protein-bound uremic toxin dialysate outlet levels increased from preinfusion 1.0 (reference) to 2.4 (1.2) for indoxyl sulfate and to 2.4 (1.0) for p-cresyl sulfate (each P<0.001). Although median serum post- and predialyzer levels in the preinfusion period were similar, infusion led to a marked drop in serum postdialyzer levels for both indoxyl sulfate and p-cresyl sulfate (-1.0 and -0.3 mg/dl, respectively; each P<0.001). The removal of the nonprotein-bound solutes creatinine and urea was not increased by the ibuprofen infusion.ConclusionsInfusion of ibuprofen into the arterial bloodline during hemodialysis significantly increases the dialytic removal of indoxyl sulfate and p-cresyl sulfate and thereby, leads to greater reduction in their serum levels.

Dataset Information

A Novel Strategy for Enhanced Sequestration of Protein-Bound Uremic Toxins Using Smart Hybrid Membranes.

Publications

A Novel Strategy for Enhanced Sequestration of Protein-Bound Uremic Toxins Using Smart Hybrid Membranes.

Similar Datasets

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