Abstract
BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is a premalignant condition characterized by somatic mutations in hematopoietic stem cells in the absence of hematologic malignancy. CHIP predominantly affects older adults and is associated with increased risks of hematologic malignancy, cardiovascular events, and all-cause mortality. However, data on the prevalence, mutational spectrum, and clinical implications of CHIP in Asian patients with end-stage kidney disease (ESKD) undergoing chronic hemodialysis remain limited. Moreover, whether specific CHIP-associated genes confer distinct clinical characteristics or prognostic implications in this population remains unclear. In this prospective study, peripheral blood samples were obtained for whole-exome sequencing to identify CHIP-associated mutations. Clonal cytopenia of undetermined significance (CCUS) was defined as the presence of CHIP in patients with persistent cytopenia without an identifiable cause. The primary outcome was all-cause mortality, while secondary outcomes included major adverse cardiovascular events and malignancy. RESULTS: 61 patients with ESKD undergoing chronic hemodialysis were included and followed for a mean of 2.1 years. CHIP-associated mutations were detected in 50 patients (81.9%), who were classified as CHIP only (n = 8) or CCUS (n = 42), while 11 patients had no CHIP or CCUS. According to the Clonal Hematopoiesis Risk Score, patients with CHIP or CCUS were further stratified into low-, intermediate-, and high-risk groups. BCORL1 was the most frequently mutated gene (24.7%), followed by GNAS, BCOR, DNMT3A, ASXL1, and ATM, and remained predominant across all risk categories. BCORL1 mutations were more prevalent than DNMT3A mutations, particularly in CCUS. Unlike DNMT3A, which showed a clear age-dependent increase, BCORL1 mutations peaked between 50 and 70 years of age. At baseline, patients with BCORL1 mutations had a higher prevalence of cardiovascular disease and lower serum albumin levels. However, overall mortality and other clinical outcomes did not differ significantly during follow-up. CONCLUSIONS: CHIP in Asian patients undergoing chronic hemodialysis shows a high prevalence and a distinct mutation spectrum dominated by BCORL1. These findings suggest disease- and ancestry-specific selective pressures beyond aging and support gene-specific risk stratification and closer hematologic surveillance. Further multi-ethnic studies are needed to define the cardiovascular and hematologic implications of BCORL1-associated CHIP.