Extended Duration Nocturnal Hemodialysis and Changes in Plasma Metabolite Profiles

Clin J Am Soc Nephrol. 2018 Mar 7;13(3):436-444. doi: 10.2215/CJN.08790817. Epub 2018 Feb 14.


Background and objectives: In-center, extended duration nocturnal hemodialysis has been associated with variable clinical benefits, but the effect of extended duration hemodialysis on many established uremic solutes and other components of the metabolome is unknown. We determined the magnitude of change in metabolite profiles for patients on extended duration nocturnal hemodialysis.

Design, setting, participants, & measurements: In a 52-week prospective, observational study, we followed 33 patients receiving conventional thrice weekly hemodialysis who converted to nocturnal hemodialysis (7-8 hours per session, three times per week). A separate group of 20 patients who remained on conventional hemodialysis (3-4 hours per session, three times per week) served as a control group. For both groups, we applied liquid chromatography-mass spectrometry-based metabolite profiling on stored plasma samples collected from all participants at baseline and after 1 year. We examined longitudinal changes in 164 metabolites among those who remained on conventional hemodialysis and those who converted to nocturnal hemodialysis using Wilcoxon rank sum tests adjusted for multiple comparisons (false discovery rate <0.05).

Results: On average, the nocturnal group had 9.6 hours more dialysis per week than the conventional group. Among 164 metabolites, none changed significantly from baseline to study end in the conventional group. Twenty-nine metabolites changed in the nocturnal group, 21 of which increased from baseline to study end (including all branched-chain amino acids). Eight metabolites decreased after conversion to nocturnal dialysis, including l-carnitine and acetylcarnitine. By contrast, several established uremic retention solutes, including p-cresol sulfate, indoxyl sulfate, and trimethylamine N-oxide, did not change with extended dialysis.

Conclusions: Across a wide array of metabolites examined, extended duration hemodialysis was associated with modest changes in the plasma metabolome, with most differences relating to metabolite increases, despite increased dialysis time. Few metabolites showed reduction with more dialysis, and no change in several established uremic toxins was observed.

Keywords: 4-cresol sulfate; Acetylcarnitine; Amino Acids, Branched-Chain; Carnitine; Chromatography, Liquid; Control Groups; Cresols; Humans; Indican; Mass Spectrometry; Metabolome; Methylamines; Oxides; Prospective Studies; Statistics, Nonparametric; Sulfates; Sulfuric Acid Esters; hemodialysis; metabolomics; nocturnal dialysis; renal dialysis; trimethylamine; uremic toxins.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcarnitine / blood
  • Adult
  • Aged
  • Amino Acids, Branched-Chain / blood
  • Case-Control Studies
  • Cresols / blood
  • Female
  • Humans
  • Indican / blood
  • Longitudinal Studies
  • Male
  • Metabolome*
  • Methylamines / blood
  • Middle Aged
  • Prospective Studies
  • Renal Dialysis / methods*
  • Renal Insufficiency, Chronic / blood*
  • Sulfuric Acid Esters / blood
  • Time Factors


  • Amino Acids, Branched-Chain
  • Cresols
  • Methylamines
  • Sulfuric Acid Esters
  • 4-cresol sulfate
  • Acetylcarnitine
  • trimethyloxamine
  • Indican