CCN2/CTGF-Driven Myocardial Fibrosis and NT-proBNP Synergy as Predictors of Mortality in Maintenance Hemodialysis

Chronic inter-dialytic volume overload and uremic inflammation activate TGF-β/Smad3 and p38 MAPK pathways, inducing connective tissue growth factors (CCN2/CTGF)-mediated fibrosis and NT-proBNP secretion from over-stretched cardiomyocytes. The combined rise in CTGF and NT-proBNP reflects myocardial fibrosis, stiffness and remodeling, predicting cardiovascular (CV) death in maintenance hemodialysis (MHD) patients. From molecular pathology to clinical translation, circulating CCN2/CTGF and NT-proBNP levels and bio-clinical data among MHD patients were measured in this prospective cohort. Multivariate Cox regression analysis identified independent predictors of mortality, which were incorporated into a composite risk-score model. The predictive performance for all-cause, CV, and sudden cardiac death (SCD) was assessed using receiver operating characteristic (ROC) survival analysis. CCN2/CTGF, NT-proBNP, age, serum albumin, MHD vintage, high-sensitivity C-reactive protein, smoking, and diabetes mellitus were significant predictors. The integrated model yielded areas under the curve of 0.91 for all-cause mortality, 0.88 for CV mortality, and 0.87 for SCD. Integrated complementary biomarkers and clinical parameters significantly improve mortality risk prediction in MHD patients. This synergistic model provides clinicians with a robust tool for early CV screening, individualized intervention, and precision management for high-risk populations.