Mass spectrometric measurement of urinary kynurenine-to-tryptophan ratio in children with and without urinary tract infection.
Clin Biochem
; 56: 83-88, 2018 Jun.
Article
in En
| MEDLINE
| ID: mdl-29679555
ABSTRACT
BACKGROUND:
Indoleamine-2,3-dioxygenase (IDO) catalyzes the first step of tryptophan (Trp) catabolism, yielding kynurenine (Kyn) metabolites. The kynurenine-to-tryptophan (K/T) ratio is used as a surrogate for biological IDO enzyme activity. IDO expression is increased during Escherichia coli urinary tract infection (UTI). Thus, our objective was to develop a method for measurement of Kyn/Trp ratio in human blood and urine and evaluate its use as a biomarker of UTI.METHODS:
A mass spectrometric method was developed to measure Trp and Kyn in serum and urine specimens. The method was applied to clinical urine specimens from symptomatic pediatric patients with laboratory-confirmed UTI or other acute conditions and from healthy controls.RESULTS:
The liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was linear to 500⯵mol/L for both Trp and Kyn. Imprecision ranged from 5 to 15% for Trp and 6-20% for Kyn. Analytical recoveries of Trp and Kyn ranged from 96 to 119% in serum and 90-97% in urine. No correlation was found between the K/T ratio and circulating IDO mass (râ¯=â¯0.110) in serum. Urinary Kyn and Trp in the pediatric test cohort demonstrated elevations in the K/T ratio in symptomatic patients with UTI (median 13.08) and without UTI (median 14.38) compared to healthy controls (median 4.93; pâ¯<â¯0.001 for both comparisons). No significant difference in K/T ratio was noted between symptomatic patients with and without UTI (pâ¯=â¯0.84).CONCLUSIONS:
Measurement of Trp and Kyn by LC-MS/MS is accurate and precise in serum and urine specimens. While urinary K/T ratio is not a specific biomarker for UTI, it may represent a general indicator of a systemic inflammatory process.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Tryptophan
/
Urinary Tract Infections
/
Kynurenine
Type of study:
Diagnostic_studies
/
Etiology_studies
/
Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
/
Infant
/
Male
Language:
En
Journal:
Clin Biochem
Year:
2018
Document type:
Article
Affiliation country:
United States