Association Between Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Outcomes in Patients on Hemodialysis

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is a condition characterized by the presence of a somatic mutation in a hematopoietic stem cell, leading to clonal expansion of blood cells in the absence of cytopenia or hematologic malignancy. Although previous studies have shown associations between CHIP and increased risks of cardiovascular disease in general population and non-dialysis CKD patients, its clinical significance in patients undergoing hemodialysis has not been investigated. Methods: In total, 383 hemodialysis patients were enrolled in this prospective multicenter cohort study. Targeted sequencing was performed to detect CHIP mutations. The primary outcome was a composite of cardiovascular events. Results: CHIP mutations were detected in 36.3% of the participants (139/383). Among the CHIP mutations, DNMT3A was the most frequently observed, identified in 48 participants (12.5%), followed by SF3B1 (29, 7.6%), TET2 (22, 5.7%), RIT1 (21, 5.5%), and ASXL1 (8, 2.1%). Patients with CHIP were older and had a higher comorbidity index than those without. Echocardiographic findings were not different across groups. In particular, DNMT3A mutations were significantly more frequent in patients with CV events (p < 0.001). In univariable Cox regression analysis, CHIP were significantly associated with an increased risk for a composite of cardiovascular events (unadjusted hazard ratio [HR] of 1.80; 95% CI of 1.10 – 2.94, p=0.017). This association remained statistically significant after adjusting for multiple confounding factors (adjusted HR of 1.87; 95% CI of 1.11 – 3.14, P=0.018). Among the CHIP-associated genes analyzed, DNMT3A showed the strongest association with adverse cardiovascular outcomes (adjusted HR of 3.23; 95% CI of 1.64 – 6.34, P<0.001). Conclusion: CHIP mutations are independently associated with an increased risk of a composite of cardiovascular events in hemodialysis patients. These findings suggest that CHIP may serve as a potential biomarker for cardiovascular risk stratification in this high-risk population.