{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:31:59Z","timestamp":1786480319934,"version":"build-2736575974"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","license":[{"start":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T00:00:00Z","timestamp":1763078400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2026,2]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n This is the first large-scale metabolomic study in genetically confirmed autosomal dominant tubulointerstitial kidney disease (ADTKD), providing a new resource for rare kidney diseases.<\/jats:p>\n <\/jats:list-item>\n \n \n ADTKD-\n UMOD<\/jats:italic>\n and ADTKD-\n MUC1<\/jats:italic>\n are metabolically indistinguishable across stages, supporting the development of unified monitoring strategies.\n <\/jats:p>\n <\/jats:list-item>\n \n The plasma kynurenine-to-tryptophan ratio increases with CKD progression, supporting its use as a noninvasive marker of inflammation in ADTKD.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n \n Metabolomic profiling has not yet been performed in autosomal dominant tubulointerstitial kidney disease (ADTKD) due to\n UMOD<\/jats:italic>\n or\n MUC1<\/jats:italic>\n mutations and could provide valuable insights into the pathophysiology of these conditions and identify the biomarkers of disease activity.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Untargeted metabolomic analysis of plasma samples was performed on a cohort comprising 40 controls, 51 individuals with ADTKD-\n UMOD<\/jats:italic>\n , and 49 individuals with ADTKD-\n MUC1<\/jats:italic>\n with CKD stages ranging from 1 to 4.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Principal component analysis and hierarchical clustering revealed that the metabolic profiles of controls and ADTKD-\n UMOD<\/jats:italic>\n and ADTKD-\n MUC1<\/jats:italic>\n patients with CKD stages 1 and 2 were similar. The metabolome was also similar between patients with ADTKD-\n UMOD<\/jats:italic>\n and ADTKD-\n MUC1<\/jats:italic>\n at each stage of CKD. Compared with stage 2 CKD, stage 3 CKD was characterized by an increased kynurenine-to-tryptophan ratio, indicating activation of indoleamine 2,3-dioxygenase, an inflammation-induced and rate-limiting enzyme of tryptophan metabolism, and increased levels of pseudouridine, 3-indoxylsulfate,\n N<\/jats:italic>\n -formylmethione,\n N<\/jats:italic>\n -acetylated amino acids, acylcarnitines, and several other metabolites. In total, 121 metabolites were identified as significantly altered in patients in stage 4 compared with controls. Enrichment analysis of this set revealed that the most significant alterations were in the biosynthesis of arginine and branched-chain amino acids, carnitine synthesis, transfer RNA metabolism, tryptophan catabolism, urea cycle, metabolism of amino acids, glucose homeostasis, and solute carrier-mediated transmembrane transport.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Patients with ADTKD-\n UMOD<\/jats:italic>\n and ADTKD-\n MUC1<\/jats:italic>\n had similar metabolomic profiles across CKD stages. Although ADTKD is a tubulointerstitial kidney disease rather than glomerular, the effects on the metabolomic pathways appear comparable with those of other forms of CKD. The kynurenine-to-tryptophan ratio appears to be a promising biomarker of ADTKD progression and will require additional study.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.34067\/kid.0000001029","type":"journal-article","created":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T17:00:11Z","timestamp":1763139611000},"page":"321-334","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Plasma Metabolites Associated with CKD Stage in Autosomal Dominant Tubulointerstitial Kidney Disease"],"prefix":"10.34067","volume":"7","author":[{"given":"Dita","family":"Mu\u0161\u00e1lkov\u00e1","sequence":"first","affiliation":[{"name":"Research Unit for Rare Diseases, Department of Pediatrics and Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech 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