Physical activity and vascular calcification in maintenance hemodialysis: the mediating role of irisin

Vascular calcification (VC) is a major determinant of cardiovascular mortality in patients undergoing maintenance hemodialysis (MHD). Although physical activity (PA) is associated with attenuated VC, the precise mechanisms underlying this association, particularly in the MHD population, remain unclear. Irisin, a myokine linked to PA and VC inhibition, is a potential mediator. However, its role in translating PA benefits to reduced VC in MHD patients is unknown.

This cross-sectional study enrolled 326 patients undergoing maintenance hemodialysis at Xuanwu Hospital Capital Medical University (2020-2023). PA volume was assessed using the International Physical Activity Questionnaire. Serum irisin levels were measured by enzyme-linked immunosorbent assay. Severe VC was defined as an abdominal aortic calcification score (AAC) ≥ 6 on lateral lumbar spine radiography. Multivariable logistic regression and restricted cubic spline models examined the independent and nonlinear associations of PA and irisin with severe VC. Causal mediation analysis estimated the proportion of the PA-VC association mediated by irisin.

Among 326 patients, those in the severe VC group (n=196) exhibited significantly lower PA levels and serum irisin compared to the non-severe group (n=130). In fully adjusted models, both higher PA (odds ratio [OR], 0.51; 95% confidence interval [CI], 0.34-0.74) and higher irisin (OR, 0.56; 95% CI, 0.37-0.83) were independently associated with lower odds of severe calcification, with significant inverse dose-response trends (P for trend <0.001). Restricted cubic spline analyses revealed a significant nonlinear relationship between irisin and calcification risk (P for nonlinearity = 0.009), while the association for PA suggested a potential plateau at higher activity volumes. These inverse associations were consistent across subgroups stratified by age, gender, Body mass index (BMI), and diabetes status (all interaction P > 0.05). Mediation analysis indicated that irisin mediated approximately 60.8% of the total association between PA and severe VC.

This study identifies independent links between physical activity, higher irisin levels, and lower severe vascular calcification risk in hemodialysis patients, with irisin mediating a major part of this association. These findings point to the importance of lifestyle and myokine pathways. Further longitudinal and interventional research is needed to confirm causality and underlying mechanisms.