Profile of plasma free amino acids, carnitine and acylcarnitines, and JAK2 mutation as potential metabolic markers in children with type 1 diabetic nephropathy.

Fifty diabetic nephropathy (DN) children with type 1 diabetes mellitus (T1DM) and 50 healthy matched controls were included. Chromatographic assays of 14 amino acids, free carnitine and 27 carnitine esters using high-performance liquid chromatography/electrospray ionization-mass spectroscopy, and genetic testing for JAK2 mutation using real-time PCR were performed. Patients had significantly lower levels of tyrosine, branched-chain amino acids (BCAAs), and BCAA/AAA (aromatic chain amino acids) ratios, glycine, arginine, ornithine, free carnitine and some carnitine esters (C5, 6, 12 and 16) and higher phenylalanine, phenylalanine/tyrosine ratio and C18 compared with the controls and in the macro-albuminuria vs. the microalbuminuria group (p < 0.05 for all) except for free carnitine. Plasma carnitine was negatively correlated with eGFR (r = -0.488, p = 0.000). There were significant positive correlations between tyrosine with UACR ratio (r = 0.296, p = 0.037). The plasma BCAA/AAA ratio showed significant negative correlations with UACR (r = -0.484, p = 0.000). There was a significantly higher frequency of the JAK2 gene mutation in diabetic nephropathy patients compared with the control group and in macro-albuminuria than the microalbuminuria group (p = 0.000) for both. When monitoring children with T1DM, plasma free amino acids and acylcarnitine profiles should be considered, especially if they have tested positive for JAK2 for the early diagnosis of DN.