RESUMO
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 (Assuntos
Predisposição Genética para Doença/genética
, Falência Renal Crônica/genética
, Triptofano/análogos & derivados
, Sistemas de Transporte de Aminoácidos Neutros/genética
, Feminino
, Variação Genética/genética
, Taxa de Filtração Glomerular/genética
, Humanos
, Falência Renal Crônica/epidemiologia
, Falência Renal Crônica/urina
, Masculino
, Glicoproteínas de Membrana/genética
, Pessoa de Meia-Idade
, Oxirredutases/genética
, Modelos de Riscos Proporcionais
, Fatores de Risco
, Triptofano/urina