GEOapplication/xmlftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE332nnn/GSE332889/primaryOK200TranscriptomicsMus musculusExpression profiling by high throughput sequencinghttps://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE332889GEOGSEfalseQuinolinic acid metabolism may mitigate AKI to CKD transitionThe transition from acute kidney injury (AKI) to chronic kidney disease (CKD) remains a significant clinical problem with unclear underlying mechanisms. Emerging evidence suggests that alterations in tryptophan metabolism, particularly in the production of downstream metabolites such as quinolinic acid (QA), play a role in renal pathophysiology. QA is a NAD⁺ biosynthesis intermediate metabolized by the enzyme quinolinate phosphoribosyltransferase (QPRT). In this study, we investigated the role of QA in the AKI-to-CKD transition using experimental mouse models and clinical observations and leveraging multiple omics approaches. Systematic metabolomic profiling identified endogenous QA as one of the most significantly elevated metabolites following folic acid-(FA) induced injury. Exogenous QA exacerbated FA-induced kidney dysfunction, demonstrated with several techniques including RNA sequencing. Conversely, aged mice deficient in QPRT showed worsened expression of kidney fibrosis markers even in absence of kidney injury, while younger littermates exhibited worsened induced kidney injury. Mice lacking QA-producing enzymes resisted experimental AKI and AKI-to-CKD progression. Multimodal spatial metabolomics analysis of human AKI kidney biopsies revealed QA accumulation in regions of inflammatory infiltration. Finally, children with CKD exhibited higher urinary QA levels compared to healthy controls. These findings underscore QA as a potential mediator of kidney injury and therapeutic target for preventing the progression from AKI to CKD.2026/05/23GSE332889GSM9754634GSM9754633GSM9754636GSM9754635GSM9754638GSM9754637GSM9754629GSM9754630GSM9754632GSM975463119057332889Mus musculus