title: High activity of indoleamine 2,3-dioxygenase is associated with renal insufficiency in Puumala hantavirus induced nephropathia epidemica.
abstract: Nephropathia epidemica (NE) is a hemorrhagic fever with renal syndrome caused by Puumala hantavirus. The severity of NE varies greatly. The aim of the present study was to evaluate whether serum indoleamine 2,3-dioxygenase (IDO) activity is associated with the severity of NE. A prospectively collected cohort of 102 consecutive patients with acute serologically confirmed NE was examined. Serum kynurenine, tryptophan, creatinine, CRP, and blood cell count were measured for up to 5 consecutive days after admission. The kynurenine to tryptophan (kyn/trp) ratio reflecting IDO activity was calculated. A maximum kyn/trp ratio >202 µmol/mmol had a sensitivity of 85% and a specificity of 75% for detecting maximum serum creatinine values >250 µmol/L by receiver operating characteristic (ROC) analysis. A maximum kyn/trp ratio >202 µmol/mmol (high IDO level) was also associated with other parameters reflecting the severity of the disease and renal impairment. Patients with high IDO levels had higher maximum serum creatinine (379 vs. 102 µmol/L, P<0.001), plasma C-reactive protein (104.1 vs. 72.1 mg/L, P=0.029), and blood leukocyte values (11.9 vs. 9.0 × 10(9) /L, P<0.001) compared to patients with kyn/trp ratio ≤ 202 µmol/mmol. They also had lower minimum urinary output (1,100 vs. 1,900 ml/day, P<0.001) and longer hospital stays (8 vs. 5 days, P<0.001). In conclusion, high serum IDO activity was associated with increased disease severity and renal impairment in NE.
authors.affiliation: Department of Internal Medicine, Tampere University Hospital, Tampere, Finland. tuula.outinen@uta.fi
authors.forename: Tuula K
authors.initials: TK
authors.lastname: Outinen
authors.forename: Satu M
authors.initials: SM
authors.lastname: Mäkelä
authors.forename: Ilpo O
authors.initials: IO
authors.lastname: Ala-Houhala
authors.forename: Heini S A
authors.initials: HS
authors.lastname: Huhtala
authors.forename: Mikko
authors.initials: M
authors.lastname: Hurme
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Libraty
authors.forename: Simo S
authors.initials: SS
authors.lastname: Oja
authors.forename: Ilkka H
authors.initials: IH
authors.lastname: Pörsti
authors.forename: Jaana T
authors.initials: JT
authors.lastname: Syrjänen
authors.forename: Antti
authors.initials: A
authors.lastname: Vaheri
authors.forename: Jukka T
authors.initials: JT
authors.lastname: Mustonen
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood*; D001772:Blood Cell Count; D002097:C-Reactive Protein / Q000032:analysis; D003404:Creatinine / Q000097:blood; D005260:Female; D006480:Hemorrhagic Fever with Renal Syndrome / Q000473:pathology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000097:blood*; D007737:Kynurenine / Q000097:blood; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D029262:Puumala virus / Q000302:isolation & purification*; D051437:Renal Insufficiency / Q000473:pathology*; D012720:Severity of Illness Index; D014364:Tryptophan / Q000097:blood; D055815:Young Adult
chemical_list: D015415:Biomarkers; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007737:Kynurenine; D014364:Tryptophan; D002097:C-Reactive Protein; D003404:Creatinine