A randomized controlled trial of alanyl-glutamine supplementation in peritoneal dialysis fluid to assess impact on biomarkers of peritoneal health

Kidney Int. 2018 Dec;94(6):1227-1237. doi: 10.1016/j.kint.2018.08.031. Epub 2018 Oct 22.


In early clinical testing, acute addition of alanyl-glutamine (AlaGln) to glucose-based peritoneal dialysis (PD) fluids restored peritoneal cellular stress responses and leukocyte function. This study was designed to test the effect of extended treatment with AlaGln-supplemented PD fluid on biomarkers of peritoneal health. In a double-blinded, randomized crossover design, stable PD patients were treated with AlaGln (8 mM) or placebo added to PD fluid for eight weeks. As primary outcome measures, dialysate cancer-antigen 125 (CA-125) appearance rate and ex vivo stimulated interleukin-6 (IL-6) release were assessed in peritoneal equilibration tests. In 8 Austrian centers, 54 patients were screened, 50 randomized, and 41 included in the full analysis set. AlaGln supplementation significantly increased CA-125 appearance rate and ex vivo stimulated IL-6 release. AlaGln supplementation also reduced peritoneal protein loss, increased ex vivo stimulated tumor necrosis factor (TNF)-α release, and reduced systemic IL-8 levels. No adverse safety signals were observed. All 4 peritonitis episodes occurred during standard PD fluid treatment. A novel AlaGln-supplemented PD fluid improves biomarkers of peritoneal membrane integrity, immune competence, and systemic inflammation compared to unsupplemented PD fluid with neutral pH and low-glucose degradation. A phase 3 trial is needed to determine the impact of AlaGln supplementation on hard clinical outcomes.

Keywords: biocompatibility; glutamine; host defense; peritoneal immune competence; peritoneal inflammation; stress response.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Austria
  • Biomarkers / analysis
  • Cross-Over Studies
  • Dialysis Solutions / chemistry*
  • Dipeptides / administration & dosage*
  • Female
  • Humans
  • Kidney Failure, Chronic / therapy*
  • Male
  • Middle Aged
  • Peritoneal Dialysis / adverse effects*
  • Peritoneum / drug effects
  • Peritoneum / pathology
  • Peritonitis / diagnosis
  • Peritonitis / etiology
  • Peritonitis / prevention & control*
  • Proof of Concept Study
  • Prospective Studies
  • Treatment Outcome


  • Biomarkers
  • Dialysis Solutions
  • Dipeptides
  • alanylglutamine