Predictive value of kynurenine pathway metabolites in patients with diabetic kidney disease

Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease (ESKD). The kynurenine pathway, responsible for tryptophan metabolism, is linked to inflammation and renal injury. This study aimed to assess the predictive value of serum tryptophan and kynurenine pathway metabolites in diagnosing DKD and differentiating disease stages in patients with type 2 diabetes mellitus (T2DM).

A total of 164 individuals (134 with T2DM and DKD, 30 healthy controls) were included in this cross-sectional study. Serum tryptophan, kynurenine, kynurenic acid, quinolinic acid, picolinic acid, 3-hydroxykynurenine, and indoleamine 2,3-dioxygenase (IDO) levels were measured using ELISA. Analyses included ANOVA, correlation, logistic regression, and ROC curves.

Tryptophan levels were significantly reduced, while kynurenine pathway metabolites were elevated in DKD patients. eGFR showed negative correlations with kynurenine, kynurenic acid, IDO, and 3-hydroxykynurenine. ROC analysis revealed kynurenic acid, IDO, and 3-hydroxykynurenine as accurate markers for DKD staging. Logistic regression identified IDO, kynurenine, and kynurenic acid as independent predictors. Kynurenine pathway metabolites, particularly kynurenic acid and IDO, exhibit high diagnostic performance for detecting and staging DKD.

Kynurenic acid, IDO, and 3-hydroxykynurenine demonstrated strong discriminative capacity across DKD stages (AUC up to 0.951), and IDO was identified as an independent predictor of DKD. These metabolites may serve as complementary biomarkers for early risk stratification in DKD.