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Mixed Matrix Membranes Adsorbers (MMMAs) for the Removal of Uremic Toxins from Dialysate.

ABSTRACT: We developed Mixed Matrix Membrane Adsorbers (MMMAs) formed by cellulose acetate and various sorbent particles (activated carbon, zeolites ZSM-5 and clinoptilolite) for the removal of urea, creatinine and uric acid from aqueous solutions, to be used in the regeneration of spent dialysate water from Hemodialysis (HD). This process would allow reducing the disproportionate amount of water consumed and permits the development of closed-loop HD devices, such as wearable artificial kidneys. The strategy of MMMAs is to combine the high permeability of porous membranes with the toxin-capturing ability of embedded particles. The water permeability of the MMMAs ranges between 600 and 1500 L/(h m2 bar). The adsorption of urea, the limiting toxin, can be improved of about nine times with respect to the pure cellulose acetate membrane. Flow experiments demonstrate the feasibility of the process in a real HD therapy session.

SUBMITTER: De Pascale M

PROVIDER: S-EPMC8878186 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Mixed Matrix Membranes Adsorbers (MMMAs) for the Removal of Uremic Toxins from Dialysate.

De Pascale Matilde M De Angelis Maria Grazia MG Boi Cristiana C

Membranes 20220209 2

We developed Mixed Matrix Membrane Adsorbers (MMMAs) formed by cellulose acetate and various sorbent particles (activated carbon, zeolites ZSM-5 and clinoptilolite) for the removal of urea, creatinine and uric acid from aqueous solutions, to be used in the regeneration of spent dialysate water from Hemodialysis (HD). This process would allow reducing the disproportionate amount of water consumed and permits the development of closed-loop HD devices, such as wearable artificial kidneys. The strat ...[more]

PMID: 35207125

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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.

Project description:Unlabelled♦AimIn this study, we investigated, and this for the different classes of uremic toxins, whether increasing dialysate volume by shifting from continuous ambulatory peritoneal dialysis (CAPD) to higher volume automated peritoneal dialysis (APD) increases total solute clearance. ♦MethodsPatients on peritoneal dialysis were randomized in a cross-over design to one 24-hour session of first a CAPD regimen (3*2 L of Physioneal 1.36% and 1*2 L of icodextrin) or APD (consisting of 5 cycles of 2 L Physioneal 1.36 and 1 cycle of 2 L Extraneal), and the other week the alternate regime, each patient serving as his/her own control. Dialysate, blood and urine samples were collected and frozen for later batch analysis of concentrations of urea, creatinine, phosphorus, uric acid, hippuric acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, indoxyl sulfate, indole acetic acid, and p-cresyl sulfate. For the protein-bound solutes, total and free fractions were determined. Total, peritoneal and renal clearance (K) and mass removal (MR) of each solute were calculated, using validated models. ♦ResultsIn 15 patients (11 male, 3 diabetics, 56 ± 16 years, 8 on CAPD, time on peritoneal dialysis 12 ± 14 months, and residual renal function of 9.9 ± 5.4 mL/min) dialysate over plasma ratio for creatinine (D/Pcrea) was 0.62 ± 0.10. Drained volume and obtained ultrafiltration were higher with APD vs CAPD (13.3 ± 0.5 L vs 8.5 ± 0.7 L and 1.3 ± 0.5 L vs 0.5 ± 0.7 L), whereas urine output was lower (1.0 ± 0.5 L vs 1.4 ± 0.6 L). Total clearance and MR tended to be higher for CAPD vs APD for all small and water soluble solutes, but mainly because of higher renal contribution, with no difference in the peritoneal contribution. For the protein-bound solutes, no differences in clearance or mass removal were observed. ♦ConclusionAlthough the drained dialysate volume nearly doubled, APD did not result in better peritoneal clearance or solute removal vs classic CAPD. APD resulted in better ultrafiltration, but at the expense of residual urinary output and clearance.

Dataset Information

Mixed Matrix Membranes Adsorbers (MMMAs) for the Removal of Uremic Toxins from Dialysate.

Publications

Mixed Matrix Membranes Adsorbers (MMMAs) for the Removal of Uremic Toxins from Dialysate.

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