RESUMEN
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 (Asunto(s)
Predisposición Genética a la Enfermedad/genética
, Fallo Renal Crónico/genética
, Triptófano/análogos & derivados
, Sistemas de Transporte de Aminoácidos Neutros/genética
, Femenino
, Variación Genética/genética
, Tasa de Filtración Glomerular/genética
, Humanos
, Fallo Renal Crónico/epidemiología
, Fallo Renal Crónico/orina
, Masculino
, Glicoproteínas de Membrana/genética
, Persona de Mediana Edad
, Oxidorreductasas/genética
, Modelos de Riesgos Proporcionales
, Factores de Riesgo
, Triptófano/orina