Urine 6-Bromotryptophan: Associations with Genetic Variants and Incident End-Stage Kidney Disease
Year: 2020
Type: article
Abstract: Higher serum 6-bromotryptophan has been associated with lower risk of chronic kidney disease (CKD) progression, implicating mechanisms beyond renal clearance. We studied genetic determinants of urine 6-bromotryptophan and its association with CKD risk factors and incident end-stage kidney disease (ESKD) in 4,843 participants of the German Chronic Kidney Disease (GCKD) study. 6-bromotryptophan was measured from urine samples using mass spectrometry. Patients with higher levels of urine 6-bromotryptophan had higher baseline estimated glomerular filtration rate (eGFR, p < 0.001). A genome-wide association study of urine 6-bromotryptophan identified two significant loci possibly related to its tubular reabsorption, SLC6A19, and its production, ERO1A, which was also associated with serum 6-bromotryptophan in an independent study. The association between urine 6-bromotryptophan and time to ESKD was assessed using Cox regression. There were 216 ESKD events after four years of follow-up. Compared with patients with undetectable levels, higher 6-bromotryptophan levels were associated with lower risk of ESKD in models unadjusted and adjusted for ESKD risk factors other than eGFR (<median level: cause-specific hazard ratio [HR] 0.70, 95% confidence interval [CI] 0.51 to 0.97; ≥median level: HR 0.50, 95% CI 0.34 to 0.74). Upon adjustment for baseline eGFR, this association became attenuated, suggesting that urine 6-bromotryptophan may represent a correlated marker of kidney health.
Source: Scientific Reports
Institutions: University of Freiburg, University of Mississippi Medical Center, University Medical Center Freiburg, Sahlgrenska University Hospital, University of Gothenburg, Metabolon (United States), The University of Texas Health Science Center at Houston, Johns Hopkins University, Friedrich-Alexander-Universität Erlangen-Nürnberg, Charité – Universitätsmedizin Berlin, Johns Hopkins Medicine
Language: English
Subfield: Nephrology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,014
Funders: U.S. Department of Health and Human Services, Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Albert-Ludwigs-Universität Freiburg, KfH-Stiftung Präventivmedizin, National Institutes of Health, National Heart, Lung, and Blood Institute, National Human Genome Research Institute, National Institute of Diabetes and Digestive and Kidney Diseases, National Center for Research Resources
Awards: G1114307781, G114216032, G1360749331, G1522370804, G1788514665, G1823732541, G2262505034, G2462410987, Institute for Clinical and Translational Research (UL1), G2780798618, G3051506083, G3204160968, GWA for Gene-Environment Interaction Effects Influencing CHD, G3744596180, G3973572274, CKDNapp - Entwicklung der Chronic Kidney Disease Nephrologist's App - Konsolidierung von Datensätzen, Generierung von klinischen input Variablen, medizinische Interpretation und Validierung, G4516765154, G4597579782, G4739409156, G4747441672, G4790942633, G4824283243, Risk of Chronic Kidney Disease Associated with GSTM1 Deletions, G508454511, G5352314984, Genome-Wide Association for Loci Influencing CHD and Other Heart, Lung and Blood, G5770678025, G5928944960, G6060132884, Verbundprojekt: Beobachtungsstudie zur chronischen Niereninsuffizienz in Deutschland (GCKD-Studie) - TP1 Studienzentrale, TP2 Regionalzentren (anteilig) und TP4 Substudie Koronarkalzifizierung (anteilig), G6739173425, G6837735701, G6902273418, G7155745631, G7535686976, G7956646258, G824087253, G8738262636, SFB 1140: Nierenerkrankungen vom Gen zum Mechanismus (KIDGEM), From GWAS loci to blood pressure genes, variants & mechanisms - Renewal, G916230891
OpenAlex ID: W3036342339