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Serum levels and removal by haemodialysis and haemodiafiltration of tryptophan-derived uremic toxins in ESKD patients

Paats, Joosep ; Adoberg, Annika ; Arund, Jürgen ; Dhondt, Annemieke ; Fernström, Anders ; Fridolin, Ivo ; Glorieux, Griet ; Leis, Liisi ; Luman, Merike and Gonzalez-Parra, Emilio , et al. (2020) In International Journal of Molecular Sciences 21(4).
Abstract

Tryptophan is an essential dietary amino acid that originates uremic toxins that contribute to end-stage kidney disease (ESKD) patient outcomes. We evaluated serum levels and removal during haemodialysis and haemodiafiltration of tryptophan and tryptophan-derived uremic toxins, indoxyl sulfate (IS) and indole acetic acid (IAA), in ESKD patients in different dialysis treatment settings. This prospective multicentre study in four European dialysis centres enrolled 78 patients with ESKD. Blood and spent dialysate samples obtained during dialysis were analysed with high-performance liquid chromatography to assess uremic solutes, their reduction ratio (RR) and total removed solute (TRS). Mean free serum tryptophan and IS concentrations... (More)

Tryptophan is an essential dietary amino acid that originates uremic toxins that contribute to end-stage kidney disease (ESKD) patient outcomes. We evaluated serum levels and removal during haemodialysis and haemodiafiltration of tryptophan and tryptophan-derived uremic toxins, indoxyl sulfate (IS) and indole acetic acid (IAA), in ESKD patients in different dialysis treatment settings. This prospective multicentre study in four European dialysis centres enrolled 78 patients with ESKD. Blood and spent dialysate samples obtained during dialysis were analysed with high-performance liquid chromatography to assess uremic solutes, their reduction ratio (RR) and total removed solute (TRS). Mean free serum tryptophan and IS concentrations increased, and concentration of IAA decreased over pre-dialysis levels (67%, 49%, −0.8%, respectively) during the first hour of dialysis. While mean serum total urea, IS and IAA concentrations decreased during dialysis (−72%, −39%, −43%, respectively), serum tryptophan levels increased, resulting in negative RR (−8%) towards the end of the dialysis session (p < 0.001), despite remarkable Trp losses in dialysate. RR and TRS values based on serum (total, free) and dialysate solute concentrations were lower for conventional low-flux dialysis (p < 0.001). High-efficiency haemodiafiltration resulted in 80% higher Trp losses than conventional low-flux dialysis, despite similar neutral Trp RR values. In conclusion, serum Trp concentrations and RR behave differently from uremic solutes IS, IAA and urea and Trp RR did not reflect dialysis Trp losses. Conventional low-flux dialysis may not adequately clear Trp-related uremic toxins while high efficiency haemodiafiltration increased Trp losses.

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keywords
Chronic kidney disease, End-stage kidney disease, Haemodiafiltration, Haemodialysis, Indole-3 acetic acid, Indoxyl sulfate, Tryptophan, Tryptophan-derived uremic toxins, Uremic toxins
in
International Journal of Molecular Sciences
volume
21
issue
4
article number
1522
publisher
MDPI AG
external identifiers
  • pmid:32102247
  • scopus:85079893233
ISSN
1661-6596
DOI
10.3390/ijms21041522
language
English
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no
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af19315a-76f8-455e-bfee-7fda05530650
date added to LUP
2020-06-29 16:32:04
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2020-06-30 03:00:02
@article{af19315a-76f8-455e-bfee-7fda05530650,
  abstract     = {<p>Tryptophan is an essential dietary amino acid that originates uremic toxins that contribute to end-stage kidney disease (ESKD) patient outcomes. We evaluated serum levels and removal during haemodialysis and haemodiafiltration of tryptophan and tryptophan-derived uremic toxins, indoxyl sulfate (IS) and indole acetic acid (IAA), in ESKD patients in different dialysis treatment settings. This prospective multicentre study in four European dialysis centres enrolled 78 patients with ESKD. Blood and spent dialysate samples obtained during dialysis were analysed with high-performance liquid chromatography to assess uremic solutes, their reduction ratio (RR) and total removed solute (TRS). Mean free serum tryptophan and IS concentrations increased, and concentration of IAA decreased over pre-dialysis levels (67%, 49%, −0.8%, respectively) during the first hour of dialysis. While mean serum total urea, IS and IAA concentrations decreased during dialysis (−72%, −39%, −43%, respectively), serum tryptophan levels increased, resulting in negative RR (−8%) towards the end of the dialysis session (p &lt; 0.001), despite remarkable Trp losses in dialysate. RR and TRS values based on serum (total, free) and dialysate solute concentrations were lower for conventional low-flux dialysis (p &lt; 0.001). High-efficiency haemodiafiltration resulted in 80% higher Trp losses than conventional low-flux dialysis, despite similar neutral Trp RR values. In conclusion, serum Trp concentrations and RR behave differently from uremic solutes IS, IAA and urea and Trp RR did not reflect dialysis Trp losses. Conventional low-flux dialysis may not adequately clear Trp-related uremic toxins while high efficiency haemodiafiltration increased Trp losses.</p>},
  author       = {Paats, Joosep and Adoberg, Annika and Arund, Jürgen and Dhondt, Annemieke and Fernström, Anders and Fridolin, Ivo and Glorieux, Griet and Leis, Liisi and Luman, Merike and Gonzalez-Parra, Emilio and Perez-Gomez, Vanessa Maria and Pilt, Kristjan and Sanchez-Ospina, Didier and Segelmark, Mårten and Uhlin, Fredrik and Ortiz, Alberto Arduan},
  issn         = {1661-6596},
  language     = {eng},
  number       = {4},
  publisher    = {MDPI AG},
  series       = {International Journal of Molecular Sciences},
  title        = {Serum levels and removal by haemodialysis and haemodiafiltration of tryptophan-derived uremic toxins in ESKD patients},
  url          = {http://dx.doi.org/10.3390/ijms21041522},
  doi          = {10.3390/ijms21041522},
  volume       = {21},
  year         = {2020},
}