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

doi:10.3390/toxins12060351

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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?

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^2,3,

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^1,*,† and

^2,3,*,†

Division of Renal Medicine and Baxter Novum, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, 141 86 Huddinge, Stockholm, Sweden

Department of Microbiology Immunology and Transplantation, Nephrology and Renal Transplantation Research Group, KU Leuven-University of Leuven, B-3000 Leuven, Belgium

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)

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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. View Full-Text

Keywords: 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. https://doi.org/10.3390/toxins12060351

AMA Style

Dai L, Meijers BK, Bammens B, de Loor H, Schurgers LJ, Qureshi AR, 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(6):351. https://doi.org/10.3390/toxins12060351

Chicago/Turabian Style

Dai, Lu, Björn K. Meijers, Bert Bammens, Henriette de Loor, Leon J. Schurgers, Abdul R. Qureshi, Peter Stenvinkel, and Pieter Evenepoel. 2020. "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 12, no. 6: 351. https://doi.org/10.3390/toxins12060351

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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?

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