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Open AccessArticle

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?

1
Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 141 86 Huddinge, Stockholm, Sweden
2
Department of Microbiology Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven-University of Leuven, B-3000 Leuven, Belgium
3
Department of Nephrology, University Hospitals Leuven, B-3000 Leuven, Belgium
4
Department of Biochemistry, Cardiovascular Research School Maastricht, Maastricht University, 6200MD Maastricht, The Netherlands
*
Authors to whom correspondence should be addressed.
Shared senior authorship.
Toxins 2020, 12(6), 351; https://doi.org/10.3390/toxins12060351
Received: 26 March 2020 / Revised: 6 May 2020 / Accepted: 22 May 2020 / Published: 27 May 2020
(This article belongs to the Section Uremic Toxins)
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. View Full-Text
Keywords: uremic toxins; sevelamer; microbial metabolism; vitamin K; end-stage kidney disease uremic toxins; sevelamer; microbial metabolism; vitamin K; end-stage kidney disease
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Dai, L.; Meijers, B.K.; Bammens, B.; de Loor, H.; Schurgers, L.J.; Qureshi, A.R.; Stenvinkel, P.; Evenepoel, P. 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? Toxins 2020, 12, 351.

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