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?

L. Dai, B.K. Meijers, B. Bammens, H. de Loor, L.J. Schurgers, A.R. Qureshi, P. Stenvinkel*, P. Evenepoel*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

9 Citations (Web of Science)

Abstract

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.
Original languageEnglish
Article number351
Number of pages11
JournalToxins
Volume12
Issue number6
DOIs
Publication statusPublished - 1 Jun 2020

Keywords

  • binding
  • calcification
  • coronary
  • deficiency
  • end-stage kidney disease
  • hemodialysis
  • microbial metabolism
  • mortality
  • phosphate binders
  • risk
  • sevelamer
  • uremic toxins
  • vitamin k
  • MORTALITY
  • CORONARY
  • RISK
  • vitamin K
  • DEFICIENCY
  • HEMODIALYSIS
  • CALCIFICATION
  • PHOSPHATE BINDERS
  • BINDING

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