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Urine 6-Bromotryptophan: Associations with Genetic Variants and Incident End-Stage Kidney Disease

Artikel i vetenskaplig tidskrift
Författare P. Sekula
A. Tin
U. T. Schultheiss
Seema Baid-Agrawal
R. P. Mohney
I. Steinbrenner
B. Yu
S. Y. Luo
E. Boerwinkle
K. U. Eckardt
J. Coresh
M. E. Grams
A. Kottgen
Publicerad i Scientific Reports
Volym 10
Nummer/häfte 1
ISSN 2045-2322
Publiceringsår 2020
Publicerad vid Institutionen för medicin
Språk en
Länkar dx.doi.org/10.1038/s41598-020-66334...
Ämnesord genome-wide association, risk, bromination, model, gckd, Science & Technology - Other Topics
Ämneskategorier Urologi och njurmedicin

Sammanfattning

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: 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.

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