In people on peritoneal dialysis, lower levels of the muscle‑helping peptide MOTS‑c in the blood and higher levels in the dialysis fluid were linked to a higher chance of muscle loss (sarcopenia). Blood MOTS‑c levels matched how well they performed on strength and movement tests, suggesting it could be a useful marker for muscle health in this group.

<i>Background and Objectives:</i> Sarcopenia is exceedingly frequent in end-stage kidney disease (ESKD) patients on dialysis, including those undergoing peritoneal dialysis (PD), and is of multifactorial origin. MOTS-c is a mitochondrial-derived peptide that promotes muscle growth whose levels are unbalanced in ESKD. In this study, we evaluated MOTS-c balance and its relationship with sarcopenia risk in an ESKD-PD cohort. <i>Materials and Methods:</i> MOTS-c was measured in serum, urine, and dialysate samples of 32 chronic PD patients. Patients were thus screened for sarcopenia risk by the SARC-F tool, anthropometric measurements, and physical performance tests. <i>Results:</i> PD patients with a very high sarcopenia risk (SARC-F &#x2265; 2) had significantly lower serum (sMOTS-c) and higher dialysate (dMOTS-c) levels, suggesting an increased peritoneal clearance of this substance (d/s MOTS-c). sMOTS-c levels were directly correlated with muscle performance in physical tests, while an opposite relationship was found with dMOTS-c and d/sMOTS-c. ROC analyses demonstrated the diagnostic potential of MOTS-c, particularly in combination with physical and anthropometric assessments, to identify PD patients at very high risk of sarcopenia. <i>Conclusions:</i> Chronic PD may negatively affect MOTS-c balance, which, in turn, may contribute to enhanced sarcopenia risk. Larger studies are needed to confirm these observations and to validate the potential utility of this substance as a biomarker for improving sarcopenia risk stratification in PD patients.