To explore the changes and significance of the tryptophan (Trp)- kynurenine (Kyn) pathway in non-dialysis patients with chronic kidney disease (CKD) stage 1-4 by liquid chromatography-mass spectrometry (LC-MS) metabolomics method.

From March 2018 to June 2018, 47 non-dialysis patients with CKD stage 1-4 from the Department of Nephrology, First Hospital Affiliated to Suzhou University were recruited, together with 30 healthy volunteers as the control group. LC-MS was used to analyze the blood samples of the subjects. Databases as Human Metabolome Database (HMDB), MassBank, and LipidMaps, etc, were used to match different metabolites of the kynurenine pathway of different CKD stages, and draw the receiver operating characteristic (ROC) curve to evaluate the sensitivity and specificity of the different metabolites. The Metaboanalyst software was used for metabolic pathway topology analysis. The ratio of Kyn to Trp (KT value) was used to express the activity of the indoleamine-2, 3-dioxygenase (IDO), a rate-limiting enzyme in the kynurenine pathway.

In comparison with those of the control, Kyn increased in CKD stage 2 (P<0.05) while kynurenic acid (KA) increased in CKD stage 3 (P<0.01). Both Kyn and KA increased with the progressive loss of renal function (P<0.01). KT value increased in CKD stage 2 (P<0.05), and also increased with the progressive loss of renal function (P<0.01). Disorder of Trp metabolism was observed in the early stage of CKD.

The Trp-Kyn pathway was enhanced in the early stage of CKD. Kyn, KA, and IDO might be used as biomarkers of both CKD early diagnosis and CKD progression.