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Removal of Protein-Bound Uremic Toxins during Hemodialysis Using a Binding Competitor.
Clin J Am Soc Nephrol. 2019 03 07; 14(3):394-402.CJ

Abstract

BACKGROUND AND OBJECTIVES

Current 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, & MEASUREMENTS

We 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.

RESULTS

We 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.

CONCLUSIONS

Infusion 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.

Authors+Show Affiliations

Division of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de Mexico, Mexico; madero.magdalena@gmail.com.Division of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de Mexico, Mexico.Renal Research Institute, Research Division, New York, New York.Renal Research Institute, Research Division, New York, New York.Renal Research Institute, Research Division, New York, New York.Biomedical and Nutritional Sciences, University of Massachusetts, Lowell, Massachusetts; and.Division of Nephrology, Instituto Nacional de Cardiología Ignacio Chávez, Ciudad de Mexico, Mexico.Biomedical and Nutritional Sciences, University of Massachusetts, Lowell, Massachusetts; and.Renal Research Institute, Research Division, New York, New York.Renal Research Institute, Research Division, New York, New York. Department of Nephrology, Icahn School of Medicine at Mount Sinai, New York, New York.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

30755453

Citation

Madero, Magdalena, et al. "Removal of Protein-Bound Uremic Toxins During Hemodialysis Using a Binding Competitor." Clinical Journal of the American Society of Nephrology : CJASN, vol. 14, no. 3, 2019, pp. 394-402.
Madero M, Cano KB, Campos I, et al. Removal of Protein-Bound Uremic Toxins during Hemodialysis Using a Binding Competitor. Clin J Am Soc Nephrol. 2019;14(3):394-402.
Madero, M., Cano, K. B., Campos, I., Tao, X., Maheshwari, V., Brown, J., Cornejo, B., Handelman, G., Thijssen, S., & Kotanko, P. (2019). Removal of Protein-Bound Uremic Toxins during Hemodialysis Using a Binding Competitor. Clinical Journal of the American Society of Nephrology : CJASN, 14(3), 394-402. https://doi.org/10.2215/CJN.05240418
Madero M, et al. Removal of Protein-Bound Uremic Toxins During Hemodialysis Using a Binding Competitor. Clin J Am Soc Nephrol. 2019 03 7;14(3):394-402. PubMed PMID: 30755453.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Removal of Protein-Bound Uremic Toxins during Hemodialysis Using a Binding Competitor. AU - Madero,Magdalena, AU - Cano,Karla B, AU - Campos,Israel, AU - Tao,Xia, AU - Maheshwari,Vaibhav, AU - Brown,Jillian, AU - Cornejo,Beatriz, AU - Handelman,Garry, AU - Thijssen,Stephan, AU - Kotanko,Peter, Y1 - 2019/02/12/ PY - 2018/04/27/received PY - 2019/01/03/accepted PY - 2020/03/07/pmc-release PY - 2019/2/14/pubmed PY - 2020/4/1/medline PY - 2019/2/14/entrez KW - Albumins KW - Binding Sites KW - Biological KW - Dialysis Solutions KW - Ibuprofen KW - Indican KW - Indoxyl sulfate KW - Sulfates KW - Toxins KW - Tryptophan KW - albumin binding competitors KW - creatinine KW - dialysis KW - dialytic removal KW - displacer infusion KW - hemodialysis KW - p-Cresyl sulfate KW - protein bound uremic toxins KW - toxin displacement KW - urea SP - 394 EP - 402 JF - Clinical journal of the American Society of Nephrology : CJASN JO - Clin J Am Soc Nephrol VL - 14 IS - 3 N2 - BACKGROUND AND OBJECTIVES: Current 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, & MEASUREMENTS: We 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. RESULTS: We 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. CONCLUSIONS: Infusion 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. SN - 1555-905X UR - https://www.unboundmedicine.com/medline/citation/30755453/Removal_of_Protein_Bound_Uremic_Toxins_during_Hemodialysis_Using_a_Binding_Competitor_ L2 - https://cjasn.asnjournals.org/cgi/pmidlookup?view=long&amp;pmid=30755453 DB - PRIME DP - Unbound Medicine ER -