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

Joosep Paats, Annika Adoberg, Jürgen Arund, Annemieke Dhondt, Anders Fernström, Ivo Fridolin, Griet Glorieux, Liisi Leis, Merike Luman, Emilio Gonzalez-Parra, Vanessa Maria Perez-Gomez, Kristjan Pilt, Didier Sanchez-Ospina, Mårten Segelmark, Fredrik Uhlin, Alberto Arduan Ortiz

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number1522
JournalInternational Journal of Molecular Sciences
Issue number4
Publication statusPublished - 2020
Externally publishedYes

Subject classification (UKÄ)

  • Urology and Nephrology

Free keywords

  • Chronic kidney disease
  • End-stage kidney disease
  • Haemodiafiltration
  • Haemodialysis
  • Indole-3 acetic acid
  • Indoxyl sulfate
  • Tryptophan
  • Tryptophan-derived uremic toxins
  • Uremic toxins


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