Abstract: Objective  To investigate the association of serum calciprotein particles (CPPs), soluble Klotho protein, and growth differentiation factor 11 (GDF11) with coronary artery calcification (CAC) and major adverse cardiovascular events (MACE) in patients undergoing maintenance hemodialysis (MHD).  Methods  A total of 179 MHD patients treated at Handan Central Hospital between January 2022 and June 2023 were enrolled. Serum levels of CPPs, Klotho, and GDF11 were measured by ELISA. Pearson correlation analysis, Kaplan-Meier survival curves, COX regression, and ROC curves were used for analysis.  Results  Compared with the non-calcification group (n=64), patients in the calcification group (n=115) had increased serum CPPs levels (t=3.949, P=0.001) and decreased levels of Klotho and GDF11 (t=6.327, 6.378, P<0.001). The 1-year MACE incidence in the low CPPs expression group (n=86) was lower than that in the high CPPs expression group (n=93) (χ2=27.225, P<0.001). The 1-year MACE incidence in the low Klotho and GDF11 expression groups (n=91, 97) was higher than that in the high Klotho and GDF11 expression groups (n=88, 82) (χ2=35.554, 37.789, P=0.005, 0.005). Patients in the MACE group (n=76) had higher age, dialysis vintage, CACs, and CPPs than those in the non-MACE group (n=103) (t/χ2=3.426, 4.351, 27.351, 8.117, P<0.001), and lower Klotho and GDF11 levels (t=7.247, 7.031, P<0.001). CPP levels showed a positive correlation with CACs (r=0.472, P<0.001), while Klotho and GDF11 levels both exhibited a negative correlation with CACs (r=-0.384 and -0.417, respectively, both P<0.001). Advanced age (HR=2.317, 95%CI=1.140～4.710), higher CACs (HR=2.031, 95%CI=1.307～3.157), and elevated CPPs (HR=1.549, 95%CI=1.191～2.014) were risk factors for MACE in MHD patients. Elevated Klotho (HR=0.614, 95%CI=0.409～0.921), GDF11 (HR=0.762, 95%CI=0.623～0.932) levels were protective factors (P<0.001). The AUC of the combined prediction of CPPs, Klotho, and GDF11 for MACE in MHD patients was 0.919, which was superior to their individual predictions (Z=3.911, 2.819, 3.831, P=0.000, 0.005, 0.000).  Conclusion  Elevated serum CPPs and reduced Klotho and GDF11 levels in MHD patients are closely associated with coronary artery calcification and MACE in MHD patients. Combined detection of these three markers may serve as an important indicator for predicting MACE.

Key words: Maintenance hemodialysis, Calciprotein particles, Soluble Klotho protein, Growth differentiation factor 11