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Abstract: SA-OR043

Association Between Urine 6-Bromotryptophan and ESKD in the German CKD Study

Session Information

  • Biomarkers in CKD
    November 09, 2019 | Location: 152, Walter E. Washington Convention Center
    Abstract Time: 05:30 PM - 05:42 PM

Category: CKD (Non-Dialysis)

  • 2101 CKD (Non-Dialysis): Epidemiology, Risk Factors, and Prevention

Authors

  • Sekula, Peggy, Medical Center - University of Freiburg, Freiburg, Germany
  • Tin, Adrienne, Johns Hopkins University, Baltimore, Maryland, United States
  • Schultheiss, Ulla T., Medical Center - University of Freiburg, Freiburg, Germany
  • Baid-Agrawal, Seema, Charité – Universitätsmedizin Berlin, Berlin, Germany
  • Mohney, Robert P., Metabolon, Inc., Durham, North Carolina, United States
  • Steinbrenner, Inga, Medical Center - University of Freiburg, Freiburg, Germany
  • Yu, Bing, University of Texas Health Science Center, Houston, Texas, United States
  • Boerwinkle, Eric, University of Texas Health Science Center, Houston, Texas, United States
  • Eckardt, Kai-Uwe, Charité – Universitätsmedizin Berlin, Berlin, Germany
  • Coresh, Josef, Johns Hopkins University, Baltimore, Maryland, United States
  • Grams, Morgan, Johns Hopkins University, Baltimore, Maryland, United States
  • Kottgen, Anna, Medical Center - University of Freiburg, Freiburg, Germany
Background

Higher serum 6-bromotryptophan has been associated with lower risk of chronic kidney disease (CKD) progression, but its levels in urine have not yet been studied. We studied determinants of urine 6-bromotryptophan and its association with CKD risk factors and incident end-stage kidney disease (ESKD) in 4,843 CKD patients.

Methods

6-bromotryptophan was measured from spot urine samples using mass spectrometry. Genetic determinants of 6-bromotryptophan levels were assessed using genome-wide association studies (GWAS) in European ancestry cohorts. The associations between urine 6-bromotryptophan and CKD risk factors were assessed by univariate tests. The risk for ESKD, defined as incident dialysis, kidney transplantation, or kidney-related death, by 6-bromotryptophan levels was assessed using Cox regression.

Results

Urine 6-bromotryptophan was detected in 57% of the patients and categorized into three groups: undetectable, low (<median), and high (≥median). GWAS of urine 6-bromotryptophan levels detected two significant loci likely related to its generation and tubular reabsorption, illuminating its biological determinants (near SLC6A19, p=3.2x10-12; near GPR137C, p=2.4x10-14). The locus near GPR137C possibly related to its generation was also associated with serum 6-bromotryptophan in an independent general population-based cohort (p=7.3x10-9). Patients with higher levels of urine 6-bromotryptophan had higher baseline estimated glomerular filtration rate (eGFR, p<0.001). After four years of follow-up, we observed 216 ESKD events. Compared with the undetectable group, higher 6-bromotryptophan levels were associated with lower risk of ESKD in unadjusted models and when adjusting for all ESKD risk factors other than eGFR (low group cause-specific hazard ratio [HR]: 0.7, 95% confidence interval [CI]: 0.51 to 0.97; high group HR: 0.5, 95% CI: 0.34 to 0.74). With the addition of baseline eGFR, this association became insignificant.

Conclusion

Higher urine 6-bromotryptophan levels were associated with lower risk of ESKD, which was attenuated when adjusting for baseline eGFR. The protective direction of association is noteworthy, because higher levels of most other metabolites, such as creatinine, are associated with higher risk of ESKD.