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Protein-Bound Uremic Toxins in Hemodialysis Patients Relate to Residual Kidney Function, Are Not Influenced by Convective Transport, and Do Not Relate to Outcome.
Toxins (Basel). 2020 04 07; 12(4)T

Abstract

Protein-bound uremic toxins (PBUTs) are predominantly excreted by renal tubular secretion and hardly removed by traditional hemodialysis (HD). Accumulation of PBUTs is proposed to contribute to the increased morbidity and mortality of patients with end-stage kidney disease (ESKD). Preserved PBUT excretion in patients with residual kidney function (RKF) and/or increased PBUT clearance with improved dialysis techniques might improve the prognosis of patients with ESKD. The aims of this study are to explore determinants of PBUTs in HD patients, and investigate whether hemodiafiltration (HDF) lowers PBUT plasma concentrations, and whether PBUTs are related to the outcome. Predialysis total plasma concentrations of kynurenine, kynurenic acid, indoxyl sulfate, indole-3-acetic acid, p-cresyl sulfate, p-cresyl glucuronide, and hippuric acid were measured by UHPLC-MS at baseline and after 6 months of follow-up in the first 80 patients participating in the CONvective TRAnsport Study (CONTRAST), a randomized controlled trial that compared the effects of online HDF versus low-flux HD on all-cause mortality and new cardiovascular events. RKF was inversely related to kynurenic acid (p < 0.001), indoxyl sulfate (p = 0.001), indole-3-acetic acid (p = 0.024), p-cresyl glucuronide (p = 0.004) and hippuric acid (p < 0.001) plasma concentrations. Only indoxyl sulfate decreased by 8.0% (-15.3 to 34.6) in patients treated with HDF and increased by 11.9% (-15.4 to 31.9) in HD patients after 6 months of follow-up (HDF vs. HD: p = 0.045). No independent associations were found between PBUT plasma concentrations and either risk of all-cause mortality or new cardiovascular events. In summary, in the current population, RKF is an important determinant of PBUT plasma concentrations in HD patients. The addition of convective transport did not consistently decrease PBUT plasma concentrations and no relation was found between PBUTs and cardiovascular endpoints.

Authors+Show Affiliations

Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands. Julius Center for Health Sciences and Primary Care, University Utrecht, 3584 CG Utrecht, The Netherlands.Julius Center for Health Sciences and Primary Care, University Utrecht, 3584 CG Utrecht, The Netherlands.Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3584 CG Utrecht, The Netherlands.Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, Nephrology, 1081 HV Amsterdam, The Netherlands.Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Cardiovascular Sciences, Nephrology, 1081 HV Amsterdam, The Netherlands.Department of Internal Medicine, Maasstad Hospital, 3079 DZ Rotterdam, The Netherlands.Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.Department of Nephrology and Hypertension, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands.

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32272776

Citation

van Gelder, Maaike K., et al. "Protein-Bound Uremic Toxins in Hemodialysis Patients Relate to Residual Kidney Function, Are Not Influenced By Convective Transport, and Do Not Relate to Outcome." Toxins, vol. 12, no. 4, 2020.
van Gelder MK, Middel IR, Vernooij RWM, et al. Protein-Bound Uremic Toxins in Hemodialysis Patients Relate to Residual Kidney Function, Are Not Influenced by Convective Transport, and Do Not Relate to Outcome. Toxins (Basel). 2020;12(4).
van Gelder, M. K., Middel, I. R., Vernooij, R. W. M., Bots, M. L., Verhaar, M. C., Masereeuw, R., Grooteman, M. P., Nubé, M. J., van den Dorpel, M. A., Blankestijn, P. J., Rookmaaker, M. B., & Gerritsen, K. G. F. (2020). Protein-Bound Uremic Toxins in Hemodialysis Patients Relate to Residual Kidney Function, Are Not Influenced by Convective Transport, and Do Not Relate to Outcome. Toxins, 12(4). https://doi.org/10.3390/toxins12040234
van Gelder MK, et al. Protein-Bound Uremic Toxins in Hemodialysis Patients Relate to Residual Kidney Function, Are Not Influenced By Convective Transport, and Do Not Relate to Outcome. Toxins (Basel). 2020 04 7;12(4) PubMed PMID: 32272776.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protein-Bound Uremic Toxins in Hemodialysis Patients Relate to Residual Kidney Function, Are Not Influenced by Convective Transport, and Do Not Relate to Outcome. AU - van Gelder,Maaike K, AU - Middel,Igor R, AU - Vernooij,Robin W M, AU - Bots,Michiel L, AU - Verhaar,Marianne C, AU - Masereeuw,Rosalinde, AU - Grooteman,Muriel P, AU - Nubé,Menso J, AU - van den Dorpel,M A, AU - Blankestijn,Peter J, AU - Rookmaaker,Maarten B, AU - Gerritsen,Karin G F, Y1 - 2020/04/07/ PY - 2020/02/04/received PY - 2020/03/31/revised PY - 2020/04/05/accepted PY - 2020/4/11/entrez PY - 2020/4/11/pubmed PY - 2021/3/3/medline KW - End-stage kidney disease KW - Protein-bound uremic toxin KW - convection KW - hemodiafiltration KW - hemodialysis KW - residual kidney function JF - Toxins JO - Toxins (Basel) VL - 12 IS - 4 N2 - Protein-bound uremic toxins (PBUTs) are predominantly excreted by renal tubular secretion and hardly removed by traditional hemodialysis (HD). Accumulation of PBUTs is proposed to contribute to the increased morbidity and mortality of patients with end-stage kidney disease (ESKD). Preserved PBUT excretion in patients with residual kidney function (RKF) and/or increased PBUT clearance with improved dialysis techniques might improve the prognosis of patients with ESKD. The aims of this study are to explore determinants of PBUTs in HD patients, and investigate whether hemodiafiltration (HDF) lowers PBUT plasma concentrations, and whether PBUTs are related to the outcome. Predialysis total plasma concentrations of kynurenine, kynurenic acid, indoxyl sulfate, indole-3-acetic acid, p-cresyl sulfate, p-cresyl glucuronide, and hippuric acid were measured by UHPLC-MS at baseline and after 6 months of follow-up in the first 80 patients participating in the CONvective TRAnsport Study (CONTRAST), a randomized controlled trial that compared the effects of online HDF versus low-flux HD on all-cause mortality and new cardiovascular events. RKF was inversely related to kynurenic acid (p < 0.001), indoxyl sulfate (p = 0.001), indole-3-acetic acid (p = 0.024), p-cresyl glucuronide (p = 0.004) and hippuric acid (p < 0.001) plasma concentrations. Only indoxyl sulfate decreased by 8.0% (-15.3 to 34.6) in patients treated with HDF and increased by 11.9% (-15.4 to 31.9) in HD patients after 6 months of follow-up (HDF vs. HD: p = 0.045). No independent associations were found between PBUT plasma concentrations and either risk of all-cause mortality or new cardiovascular events. In summary, in the current population, RKF is an important determinant of PBUT plasma concentrations in HD patients. The addition of convective transport did not consistently decrease PBUT plasma concentrations and no relation was found between PBUTs and cardiovascular endpoints. SN - 2072-6651 UR - https://www.unboundmedicine.com/medline/citation/32272776/Protein_Bound_Uremic_Toxins_in_Hemodialysis_Patients_Relate_to_Residual_Kidney_Function_Are_Not_Influenced_by_Convective_Transport_and_Do_Not_Relate_to_Outcome_ L2 - https://www.mdpi.com/resolver?pii=toxins12040234 DB - PRIME DP - Unbound Medicine ER -