title: Tryptophan and Kynurenine Levels and Its Association With Sleep, Nonphysical Fatigue, and Depression in Chronic Hemodialysis Patients.
abstract: Sleep and mood disorders are common in hemodialysis (HD) patients and the pathophysiology is still unclear. Tryptophan (TRP) and its metabolites may play a prominent role in neural pathways related to sleep, fatigue, and depression. Here, we sought to compare the levels of TRP and its metabolites between HD patients and healthy subjects and examine their association with sleep, fatigue, and depression in HD patients. The design was cross-sectional analysis.
  
  
  
  Ninety-nine adult patients on stable thrice weekly HD schedule between September 2011 and March 2014 and 10 healthy controls.
  
  
  
  Venous blood samples were drawn in healthy subjects and immediately before dialysis in chronic HD patients. TRP and kynurenine (KYN) metabolites were measured by high-performance liquid chromatography. The Medical Outcomes Study Sleep Scale, the PROMIS Short form Fatigue, and the Patient Health Questionnaire were administered concurrently.
  
  
  
  Sleep, fatigue, and depression as assessed by subjective questionnaire.
  
  
  
  TRP levels were significantly lower (52.4 ± 15.2 vs. 67.9 ± 3.1 μmol/L; P < .0001) and KYN (3.2 ± 1.2 vs. 1.4 ± 0.1 μmol/L; P < .0001) were significantly higher in the 99 HD patients relative to 10 healthy controls. In HD patients, higher KYN levels were correlated with worse depression and fatigue scores (r2= 0.23 and 0.21; P ≤ .05, respectively). We found no association between TRP and KYN/TRP ratio with sleep disturbances, fatigue, and depression in HD patients.
  
  
  
  Our study indicates disturbed TRP metabolism in HD patients, but low TRP levels were not related with sleep disturbances, depression, and fatigue. In contrast, KYN levels, a metabolite of TRP, were much higher in HD patients compared with controls, and higher KYN associated with depression and fatigue. Further studies exploring the biological and functional consequences of increased TRP catabolism in HD patients are warranted.
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of California at San Diego, San Diego, California.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Malhotra
authors.affiliation: Division of Nephrology, Department of Medicine, University Medical Center Ljubljana, Ljubljana, Slovenia.
authors.forename: Vanja
authors.initials: V
authors.lastname: Persic
authors.affiliation: Clinical Laboratory and Nutritional Sciences, University of Massachusetts Lowell, Lowell, Massachusetts.
authors.forename: Weifang
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Clinical Laboratory and Nutritional Sciences, University of Massachusetts Lowell, Lowell, Massachusetts.
authors.forename: Jill
authors.initials: J
authors.lastname: Brown
authors.affiliation: Clinical Laboratory and Nutritional Sciences, University of Massachusetts Lowell, Lowell, Massachusetts; Renal Research Institute, New York, New York.
authors.forename: Xia
authors.initials: X
authors.lastname: Tao
authors.affiliation: Renal Research Institute, New York, New York.
authors.forename: Laura
authors.initials: L
authors.lastname: Rosales
authors.affiliation: Renal Research Institute, New York, New York.
authors.forename: Stephan
authors.initials: S
authors.lastname: Thijssen
authors.affiliation: Division of Nephrology, Department of Medicine, Yale University School of Medicine, New Haven, Connecticut.
authors.forename: Fredric O
authors.initials: FO
authors.lastname: Finkelstein
authors.affiliation: Division of Nephrology, Department of Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Unruh
authors.affiliation: Division of Nephrology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
authors.forename: Alp
authors.initials: A
authors.lastname: Ikizler
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of California at San Diego, San Diego, California.
authors.forename: Pranav S
authors.initials: PS
authors.lastname: Garimella
authors.affiliation: Division of Nephrology and Hypertension, Department of Medicine, University of California at San Diego, San Diego, California.
authors.forename: Joachim H
authors.initials: JH
authors.lastname: Ix
authors.affiliation: Division of Nephrology, Department of Medicine, University Hospital Maastricht, Maastricht, the Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Kooman
authors.affiliation: Renal Research Institute, New York, New York.
authors.forename: Nathan W
authors.initials: NW
authors.lastname: Levin
authors.affiliation: Clinical Laboratory and Nutritional Sciences, University of Massachusetts Lowell, Lowell, Massachusetts.
authors.forename: Garry J
authors.initials: GJ
authors.lastname: Handelman
authors.affiliation: Renal Research Institute, New York, New York; Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: pkotanko@rriny.com.
authors.forename: Peter
authors.initials: P
authors.lastname: Kotanko
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003863:Depression / Q000097:blood* / Q000175:diagnosis; D005221:Fatigue / Q000097:blood* / Q000175:diagnosis; D005260:Female; D006801:Humans; D007737:Kynurenine / Q000097:blood*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D015203:Reproducibility of Results; D012890:Sleep / Q000502:physiology*; D011795:Surveys and Questionnaires; D014364:Tryptophan / Q000097:blood*
chemical_list: D007737:Kynurenine; D014364:Tryptophan