Effect of chronic kidney disease and type 2 diabetes on plasma branched-chain amino acid cross-correlation: a novel metric for evaluating homeostasis

Cross-correlations between plasma isoleucine (Ile), leucine (Leu), and valine (Val) concentrations are observed in healthy individuals (C group). A parallel shift in these correlations has been noted in patients with end-stage renal failure. To evaluate this shift, a novel b value metric is proposed to assess variations in individuals. Branched-chain amino acids (BCAAs) concentrations were analyzed in four groups: 69 healthy controls (C group), 97 patients with type 2 diabetes mellitus (T2DM), 63 patients with chronic kidney disease (CKD) not on hemodialysis (CKD), and 45 patients with CKD on hemodialysis (CKD-HD). The b value was calculated using the equation Y = aX + b, where coefficient a was derived from the regression line in the C, and each BCAA pair (X, Y) was substituted accordingly. The T2DM exhibited elevated BCAA levels; however, the b values for the (Ile, Leu) and (Ile, Val) pairs remained unchanged. The CKD and CKD-HD showed significant decreases in b values. In T2DM, increased BCAA levels followed the regression line observed in healthy individuals, whereas in CKD, decreased BCAA levels deviated from this pattern. The b value effectively detects changes in BCAA metabolism that are not captured by individual BCAA levels alone, serving as a novel indicator of altered BCAA metabolism and homeostasis.