MOTS-c is associated with oxidative stress and arterial stiffness in peritoneal dialysis patients: a pilot study

Purpose Oxidative stress (OS) and endothelial dysfunction are major drivers of cardiovascular disease (CVD) in peritoneal dialysis (PD). MOTS-c, a mitochondria-derived peptide, is emerging as a key regulator of skeletal muscle health, metabolic homeostasis, and vascular function, yet its role in the uremic environment remains unexplored. We investigated the relationship between MOTS-c levels, OS markers, and vascular stiffness in PD patients. Methods This pilot, clinical study included 32 stable PD patients (mean age 60.7 +/- 1.2 years, 62.5% male). MOTS-c levels were quantified in serum (sMOTS-c), urine (uMOTS-c), and peritoneal dialysate (dMOTS-c). Systemic oxidative status was assessed via plasma Advanced Oxidation Protein Products (AOPPs). Vascular function was evaluated by carotid-femoral Pulse Wave Velocity (PWV), and left ventricular systolic function was assessed echocardiographically. Results Urinary MOTS-c (uMOTS-c) levels were inversely correlated with serum AOPPs (R = - 0.592, p = 0.012) and a positive association with PWV (R = 0.708, p = 0.001) and left ventricular systolic function (R = 0.440, p = 0.04). Conversely, dialysate MOTS-c (dMOTS-c) were strongly and inversely correlated with PWV (R = - 0.717, p = 0.019) as well as systolic and diastolic blood pressure (R =-0.5, p < 0.01). Conclusion Eta igher urinary MOTS-c was linked to lower systemic oxidative stress, suggesting a potential protective role, and associated with greater arterial stiffness, potentially reflecting a compensatory response to vascular injury. In contrast, higher peritoneal MOTS-c levels were associated with an improved vascular profile. These findings suggest a novel 'Mitochondrial-Vascular Axis' in uremia, highlighting MOTS-c as a potential biomarker.