The Role of Tryptophan Metabolism in the Occurrence and Progression of Acute and Chronic Kidney Diseases.

Abstract

Acute kidney injury (AKI) and chronic kidney disease (CKD) are common kidney diseases in clinics with high morbidity and mortality, but their pathogenesis is intricate. Tryptophan (Trp) is a fundamental amino acid for humans, and its metabolism produces various bioactive substances involved in the pathophysiology of AKI and CKD. Metabolomic studies manifestthat Trp metabolites like kynurenine (KYN), 5-hydroxyindoleacetic acid (5-HIAA), and indoxyl sulfate (IS) increasein AKI or CKD and act as biomarkers that facilitate the early identification of diseases. Meanwhile, KYN and IS act as ligands to exacerbate kidney damage by activating aryl hydrocarbon receptor (AhR) signal transduction. The reduction of renal function can cause the accumulation of Trp metabolites which in turn accelerate the progression of AKI or CKD. Besides, gut dysbiosis induces the expansion of Enterobacteriaceae family to produce excessive IS, which cannot be excreted due to the deterioration of renal function. The application of Trp metabolism as a target in AKI and CKD will also be elaborated. Thus, this studyaims to elucidate Trp metabolism in the development of AKI and CKD, and explores the relative treatment strategies by targeting Trp from the perspective of metabolomics to provide a reference for their diagnosis and prevention.