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Publication Information

PubMed ID
Public Release Type
Journal
Publication Year
2020
Authors
Sekula Peggy, Tin Adrienne, Schultheiss Ulla T., Baid-Agrawal Seema, Mohney Robert P., Steinbrenner Inga, Yu Bing, Luo Shengyuan, Boerwinkle Eric, Eckardt Kai-Uwe, Coresh Josef, Grams Morgan E., Kӧttgen Anna
Studies

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.