Urinary MOTS-c inversely correlates with oxidative stress, positively with arterial stiffness in PD patients

Patients undergoing peritoneal dialysis (PD) face a high risk of cardiovascular disease (CVD), largely driven by chronic oxidative stress (OS) and endothelial dysfunction. Current standard-of-care primarily manages symptoms, but novel biomarkers and therapeutic targets are needed to mitigate these complications. MOTS-c, a mitochondria-derived peptide, is gaining recognition for its roles in metabolic homeostasis and vascular function. However, its specific involvement and potential utility within the unique uremic environment of PD patients, particularly concerning OS and vascular health, remain largely unexplored, representing a critical knowledge gap this study addresses.

This pilot, clinical study included 32 stable peritoneal dialysis (PD) patients (mean age 60.7 ± 1.2 years, 62.5% male). Researchers quantified MOTS-c levels in serum (sMOTS-c), urine (uMOTS-c), and peritoneal dialysate (dMOTS-c). Systemic oxidative status was assessed by measuring plasma Advanced Oxidation Protein Products (AOPPs). Vascular function was evaluated using carotid-femoral Pulse Wave Velocity (PWV), a key indicator of arterial stiffness. Left ventricular systolic function was also assessed via echocardiography to provide a comprehensive cardiovascular profile.

The study revealed distinct associations between MOTS-c levels and cardiovascular markers. Urinary MOTS-c (uMOTS-c) levels were inversely correlated with serum AOPPs (R = - 0.592, p = 0.012), suggesting a potential protective role against systemic oxidative stress. However, uMOTS-c also showed a positive association with PWV (R = 0.708, p = 0.001), indicating a link to greater arterial stiffness, and with left ventricular systolic function (R = 0.440, p = 0.04). Conversely, dialysate MOTS-c (dMOTS-c) levels presented a more favorable profile: dMOTS-c were strongly and inversely correlated with PWV (R = - 0.717, p = 0.019), implying higher peritoneal MOTS-c is associated with reduced arterial stiffness. Furthermore, dMOTS-c levels were inversely correlated with both systolic and diastolic blood pressure (R = -0.5, p < 0.01), reinforcing its association with an improved vascular profile in PD patients.