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Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction?

Gut microbial metabolism is not only an important source of uremic toxins but may also help to maintain the vitamin K stores of the host. We hypothesized that sevelamer therapy, a commonly used phosphate binder in patients with end-stage kidney disease (ESKD), associates with a disturbed gut microbi...

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Autores principales: Dai, Lu, Meijers, Björn K., Bammens, Bert, de Loor, Henriette, Schurgers, Leon J., Qureshi, Abdul Rashid, Stenvinkel, Peter, Evenepoel, Pieter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354623/
https://www.ncbi.nlm.nih.gov/pubmed/32471179
http://dx.doi.org/10.3390/toxins12060351
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author Dai, Lu
Meijers, Björn K.
Bammens, Bert
de Loor, Henriette
Schurgers, Leon J.
Qureshi, Abdul Rashid
Stenvinkel, Peter
Evenepoel, Pieter
author_facet Dai, Lu
Meijers, Björn K.
Bammens, Bert
de Loor, Henriette
Schurgers, Leon J.
Qureshi, Abdul Rashid
Stenvinkel, Peter
Evenepoel, Pieter
author_sort Dai, Lu
collection PubMed
description Gut microbial metabolism is not only an important source of uremic toxins but may also help to maintain the vitamin K stores of the host. We hypothesized that sevelamer therapy, a commonly used phosphate binder in patients with end-stage kidney disease (ESKD), associates with a disturbed gut microbial metabolism. Important representatives of gut-derived uremic toxins, including indoxyl sulfate (IndS), p-Cresyl sulfate (pCS), trimethylamine N-oxide (TMAO), phenylacetylglutamine (PAG) and non-phosphorylated, uncarboxylated matrix-Gla protein (dp-ucMGP; a marker of vitamin K status), were analyzed in blood samples from 423 patients (65% males, median age 54 years) with ESKD. Demographics and laboratory data were extracted from electronic files. Sevelamer users (n = 172, 41%) were characterized by higher phosphate, IndS, TMAO, PAG and dp-ucMGP levels compared to non-users. Sevelamer was significantly associated with increased IndS, PAG and dp-ucMGP levels, independent of age, sex, calcium-containing phosphate binder, cohort, phosphate, creatinine and dialysis vintage. High dp-ucMGP levels, reflecting vitamin K deficiency, were independently and positively associated with PAG and TMAO levels. Sevelamer therapy associates with an unfavorable gut microbial metabolism pattern. Although the observational design precludes causal inference, present findings implicate a disturbed microbial metabolism and vitamin K deficiency as potential trade-offs of sevelamer therapy.
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spelling pubmed-73546232020-07-23 Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction? Dai, Lu Meijers, Björn K. Bammens, Bert de Loor, Henriette Schurgers, Leon J. Qureshi, Abdul Rashid Stenvinkel, Peter Evenepoel, Pieter Toxins (Basel) Article Gut microbial metabolism is not only an important source of uremic toxins but may also help to maintain the vitamin K stores of the host. We hypothesized that sevelamer therapy, a commonly used phosphate binder in patients with end-stage kidney disease (ESKD), associates with a disturbed gut microbial metabolism. Important representatives of gut-derived uremic toxins, including indoxyl sulfate (IndS), p-Cresyl sulfate (pCS), trimethylamine N-oxide (TMAO), phenylacetylglutamine (PAG) and non-phosphorylated, uncarboxylated matrix-Gla protein (dp-ucMGP; a marker of vitamin K status), were analyzed in blood samples from 423 patients (65% males, median age 54 years) with ESKD. Demographics and laboratory data were extracted from electronic files. Sevelamer users (n = 172, 41%) were characterized by higher phosphate, IndS, TMAO, PAG and dp-ucMGP levels compared to non-users. Sevelamer was significantly associated with increased IndS, PAG and dp-ucMGP levels, independent of age, sex, calcium-containing phosphate binder, cohort, phosphate, creatinine and dialysis vintage. High dp-ucMGP levels, reflecting vitamin K deficiency, were independently and positively associated with PAG and TMAO levels. Sevelamer therapy associates with an unfavorable gut microbial metabolism pattern. Although the observational design precludes causal inference, present findings implicate a disturbed microbial metabolism and vitamin K deficiency as potential trade-offs of sevelamer therapy. MDPI 2020-05-27 /pmc/articles/PMC7354623/ /pubmed/32471179 http://dx.doi.org/10.3390/toxins12060351 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Dai, Lu
Meijers, Björn K.
Bammens, Bert
de Loor, Henriette
Schurgers, Leon J.
Qureshi, Abdul Rashid
Stenvinkel, Peter
Evenepoel, Pieter
Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction?
title Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction?
title_full Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction?
title_fullStr Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction?
title_full_unstemmed Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction?
title_short Sevelamer Use in End-Stage Kidney Disease (ESKD) Patients Associates with Poor Vitamin K Status and High Levels of Gut-Derived Uremic Toxins: A Drug–Bug Interaction?
title_sort sevelamer use in end-stage kidney disease (eskd) patients associates with poor vitamin k status and high levels of gut-derived uremic toxins: a drug–bug interaction?
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7354623/
https://www.ncbi.nlm.nih.gov/pubmed/32471179
http://dx.doi.org/10.3390/toxins12060351
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