Alterations of Tryptophan Metabolism Pathways in Immunoglobulin A Nephropathy: an Exploratory Study

Abstract

Objective: Dysregulation of tryptophan metabolism can play a significant role in the pathogenesis of various diseases, including chronic kidney diseases, among which immunoglobulin A nephropathy (IgAN) is the most common form of primary glomerulopathy in young and middle-aged people. Analysis of tryptophan metabolism disorders may be useful for precision diagnosis of IgAN and identification of additional molecular targets for disease therapy. Methods: High-performance liquid chromatography with mass spectrometric detection was used to measure the concentrations of tryptophan and its metabolites: 5-hydroxytryptophan, kynurenine, kynurenic, indoleacetic, and indolelactic acids in blood serum samples from patients diagnosed with IgAN with disease activity (IgAN-A, n = 85) and in remission (IgAN-R, n = 28), as well as in blood serum samples from healthy volunteers (K1, n = 33) and patients with other kidney diseases (K2, n = 31). Untargeted and targeted metabolomic analysis were performed. Results and Discussion: Untargeted and targeted metabolomic analysis showed that significant changes in tryptophan metabolism in IgAN are associated with activation of the kynurenine and serotonin pathways. Conclusions: The conducted exploratory study indicates the need for additional research to study the relationship between the pathogenesis of IgAN and tryptophan metabolism.