Plasma branched-chain amino acids in chronic kidney disease: associations with atherogenic lipids and mortality

Branched-chain amino acids (BCAAs) are essential nutrients that promote muscle protein anabolism but also associate with cardiometabolic diseases; however, their role in chronic kidney disease (CKD) remains unclear. We investigated plasma BCAA levels and their associations with metabolic parameters and survival in CKD patients. Plasma BCAA levels, along with clinical and laboratory parameters, were measured in 328 patients with CKD stage 5 (median age 54 years, 60% males). BCAA concentrations in 83 community-dwelling controls (median age 51 years, 66% males) served as comparators. Multivariate linear regression analysis was employed to identify predictors of BCAA levels. Competing risk regression analysis was conducted to assess 5-year risk of all-cause and cardiovascular mortality in relation to total and individual BCAAs (valine, isoleucine, and leucine). Plasma BCAA levels were lower compared to controls (P < 0.0001) and positively associated with triglycerides and the atherogenic index of plasma, while inversely associated with high density lipoprotein-cholesterol (HDL-C), Apo-A, and Lp (a). After adjustments for confounders, low vs. high tertile of total BCAAs associated with increased risk of cardiovascular mortality (sub-hazard ratio [sHR] 2.37, 95% confidence interval [CI], 1.08-5.21) and low tertile of valine associated with higher risk of both all-cause mortality (sHR 2.05, 95% CI 1.10-3.79) and cardiovascular mortality (sHR 2.46, 95% CI 1.15-5.26). In CKD, higher levels of BCAAs associated with an atherogenic lipid profile while lower BCAAs levels associated with increased cardiovascular mortality risk, and low valine was associated with higher both all-cause and cardiovascular mortality risk. Monitoring and potentially modulating BCAA levels could have prognostic or therapeutic implications in advanced CKD.