title: Increased indoleamine 2,3-dioxygenase (IDO) activity and elevated serum levels of tryptophan catabolites in patients with chronic kidney disease: a possible link between chronic inflammation and uraemic symptoms.
abstract: BACKGROUND
  Tryptophan (Trp) is catabolized by indoleamine 2,3-dioxygenase (IDO). Changes in Trp metabolism and IDO activity in chronic kidney disease (CKD) have not been widely studied, and the impact of haemodialysis is uncertain. Here we investigate Trp catabolism, IDO activity and the role of inflammation in moderate to very severe CKD and haemodialysis.
  
  
  METHODS
  Eighty individuals were included in a prospective blinded endpoint analysis. Using tandem mass spectrometry, serum levels of Trp, kynurenine (Kyn), kynurenic-acid (Kyna), quinolinic-acid (Quin), 5-hydroxytryptophan (OH-Trp), serotonin (5-HT), estimated IDO activity and inflammatory markers were assessed in 40 CKD patients (age 57 +/- 14 years, 21 male, creatinine 4.5 +/- 2.7, n = 17 receiving haemodialysis), and in 40 healthy controls (age 34 +/- 9 years, 26 male).
  
  
  RESULTS
  Trp levels were unchanged in CKD (P = 0.78 versus controls). Serum levels of Kyn, Kyna and Quin increased with CKD severity (stages 4, 5 versus controls all P < or = 0.01). IDO activity was significantly induced in CKD and correlated with disease severity (stages 3-5 versus controls, all P < or = 0.01) and inflammatory markers [high-sensitivity C-reactive protein (hsCRP), soluble TNF-receptor-1 (sTNFR-I); both P < or = 0.03]. IDO products (Kyn, Kyna, Quin) correlated also with hsCRP and sTNFR-I (all P < or = 0.04). Haemodialysis did not influence IDO activity (P = 0.26) and incompletely removed Kyn, Kyna, Quin, OH-Trp and 5-HT by 22, 26, 50, 44 and 34%, respectively. In multiple regression, IDO activity correlated with hsCRP and sTNFR-I (both P < or = 0.03) independent of serum creatinine, age and body weight.
  
  
  CONCLUSIONS
  IDO activity and serum levels of tryptophan catabolites of the kynurenine pathway increase with CKD severity. In CKD, induction of IDO may primarily be a consequence of chronic inflammation.
authors.affiliation: Department of Nephrology and Intensive Care, Charité University Medicine, Campus Virchow Clinic, Berlin, Germany. schefold@charite.de
authors.forename: Jörg C
authors.initials: JC
authors.lastname: Schefold
authors.forename: Jan-Philip
authors.initials: JP
authors.lastname: Zeden
authors.forename: Christina
authors.initials: C
authors.lastname: Fotopoulou
authors.forename: Stephan
authors.initials: S
authors.lastname: von Haehling
authors.forename: Rene
authors.initials: R
authors.lastname: Pschowski
authors.forename: Dietrich
authors.initials: D
authors.lastname: Hasper
authors.forename: Hans-Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Christine
authors.initials: C
authors.lastname: Schuett
authors.forename: Petra
authors.initials: P
authors.lastname: Reinke
mesh_terms: D006916:5-Hydroxytryptophan / Q000097:blood; D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000097:blood*; D007249:Inflammation / Q000097:blood / Q000201:enzymology; D018836:Inflammation Mediators / Q000097:blood; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000201:enzymology / Q000628:therapy; D007736:Kynurenic Acid / Q000097:blood; D007737:Kynurenine / Q000097:blood; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D017378:Quinolinic Acid / Q000097:blood; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D006435:Renal Dialysis; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000201:enzymology; D012701:Serotonin / Q000097:blood; D014364:Tryptophan / Q000097:blood*; D014511:Uremia / Q000097:blood / Q000201:enzymology
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D018836:Inflammation Mediators; D047888:Receptors, Tumor Necrosis Factor, Type I; D012701:Serotonin; D007737:Kynurenine; D014364:Tryptophan; D002097:C-Reactive Protein; D003404:Creatinine; D006916:5-Hydroxytryptophan; D017378:Quinolinic Acid; D007736:Kynurenic Acid