The non-linear associations between blood manganese level and sarcopenia in patients undergoing maintenance hemodialysis: A multicenter cross-sectional study

Background and aims: Manganese (Mn), a vital element in energy metabolism, is predominantly stored in skeletal muscles and plays a crucial role in muscle function and strength. Patients on maintenance hemodialysis (MHD) often experience muscle wasting due to metabolic disruption and inflammation. This study aimed to explore the relationship between blood Mn levels and sarcopenia in a patient population. Methods: In this multicenter cross-sectional study, conducted from March 2021 to March 2022, 386 patients on MHD from three medical centers were included. Blood Mn levels were measured using inductively coupled plasma mass spectrometry, and body composition was assessed post -dialysis using bioelectrical impedance analysis. Grip strength was measured using a digital dynamometer. The patients were categorized into groups with and without sarcopenia. Using a generalized additive model to fit a smooth curve, we employed a generalized linear model to identify the optimal inflection point and explore the threshold effect after discovering a segmented relationship. Subsequently, a binary logistic regression analysis was conducted to investigate the relationship between blood manganese levels and the risk of sarcopenia, with adjustments made for potential confounding factors. Results: A negative correlation was observed between blood Mn levels and sarcopenia-related parameters (Appendicular Skeletal Muscle Mass Index and grip strength) in Spearman 's correlation analysis (both P < 0.05). After adjusting for confounding factors, a nonlinear association was identified. When blood Mn was <= 10.6 g/L, the increase in sarcopenia was not statistically significant (P > 0.05). Conversely, when blood Mn exceeded 10.6 mu g/L, each 1 mu g/L increase raised the risk of sarcopenia by 0.1 times. Considering confounders, multivariate binary logistic regression confirmed an independent association between elevated blood Mn levels and sarcopenia. Conclusion: This study revealed an independent association between elevated blood Mn levels ( > 10.6 mu g/L) and sarcopenia in patients undergoing MHD. These findings emphasize the importance of understanding the Mn metabolism in the context of muscle health in this patient population. Further research is warranted to explore the underlying mechanisms and potential interventions for mitigating sarcopenia in patients with elevated blood Mn levels undergoing MHD.