<b>Urine branched-chain amino acid excretion and chronic kidney disease progression in patients with type 2 diabetes</b>

<p dir="ltr">Preclinical studies suggest that activating branched chain amino acid (BCAA) catabolism may improve chronic kidney disease (CKD). In this prospective clinical study, we sought to examine the association between urine BCAA excretion and risk of CKD progression in patients with type 2 diabetes. Baseline urine BCAAs were measured by mass spectrometry in 1868 outpatients with type 2 diabetes. The study outcome was a composite of end stage kidney disease (ESKD, eGFR <15 ml/min/1.73m2, dialysis, renal death) or doubling of serum creatinine. During a median of 7.2 years of follow-up, 203 renal events were identified. One SD increment in urine valine, leucine and isoleucine concentration was associated with 1.29 (95% CI 1.11-1.51), 1.31 (1.11-1.55) and 1.29 (1.09-1.53) folds increased risk for the composite renal outcome after adjustment for clinical risk factors. Mediation analysis showed that urine monocyte chemoattractant protein-1 mediated 57%, 47% and 58% of the effects of valine, leucine and isoleucine on renal outcome, respectively. High levels of urine BCAAs were also independently associated with an increased risk of CKD progression in Chronic Renal Insufficiency Cohort in United States. Our data suggest that dysregulation of BCAA metabolism in kidney may be involved in intrarenal inflammation and drive CKD progression.</p>