Carnitine dysregulation in diabetic kidney disease: from pathogenic mechanism to precision biomarker.

Carnitine is essential for mitochondrial fatty acid β-oxidation and redox homeostasis, and mounting evidence shows that carnitine metabolism is profoundly perturbed in diabetic kidney disease (DKD). These abnormalities were previously regarded as secondary epiphenomena of metabolic dysfunction, but accumulating evidence now indicates that they arise from hyperglycaemia-driven OCTN2 impairment, insulin resistance, and oxidative stress, together forming a distinct carnitine-related metabolic signature. Plasma acylcarnitine profiles generally provide more robust and reproducible indicators of systemic metabolic disturbance, and selected signatures may outperform the urinary albumin-to-creatinine ratio (UACR) in the early detection of DKD. By contrast, urinary carnitine changes reflect early defects in proximal tubular reabsorption, supporting kidney-specific phenotyping. Accordingly, integrated plasma and urinary profiling may enhance early detection, facilitate risk stratification, and support treatment monitoring. However, interpretation of these signatures may be confounded by kidney function and medication use, and clinical translation will require rigorous external validation, particularly in prospective cohorts and trials specifically designed for DKD.