Clonal Hematopoiesis and Cardiovascular Events in Patients with ESKD on Hemodialysis

Key Points The prevalence of clonal hematopoiesis in patients with ESKD on hemodialysis was 7%. Clonal hematopoiesis was not associated with stroke, myocardial infarction, or venous thromboembolism. Clonal hematopoiesis was associated with vascular access thrombosis. Background Patients with ESKD on hemodialysis are at high risk for cardiovascular complications. Clonal hematopoiesis (CH), defined as clonal expansion of hematopoietic stem cells due to acquired mutations, was shown to be associated with cardiovascular events, but this association was not yet assessed in patients with impaired kidney function. Methods Our aim was to investigate the CH-associated mutation prevalence in patients with ESKD on hemodialysis included in the population-based prospective observational Vienna InVestigation of AtriaL Fibrillation and thromboembolism in hemoDIalysis (VIVALDI) study and to assess an association between CH and cardiovascular outcomes. Peripheral blood DNA samples collected at study inclusion were screened for CH-associated mutations. Results Five hundred seventy patients were analyzed (median age, 66 years [interquartile range [IQR], 55–75]; 37.1% female). The median follow-up time was 39 months (IQR, 35–41). We detected 44 CH-associated variants in 40 patients (7%), most commonly in the gene DNMT3A (43%), TET2 (18%), and TP53 (18%). Patients with CH were older (75 [IQR, 68–80] versus 65 [IQR, 54–74] years, P < 0.001) and had longer cumulative dialysis time (4 [IQR, 1.0–4.0] versus 2 [IQR, 1.9–5.5] years, P = 0.02). CH was not associated with stroke (subdistribution hazard ratio [SHR], 0.25; 95% confidence interval [CI], 0.04 to 1.84), myocardial infarction (SHR, 0.90; 95% CI, 0.20 to 4.13), three-point major adverse cardiovascular events (SHR, 0.65; 95% CI, 0.33 to 1.28), or venous thromboembolism (SHR, 1.68; 95% CI, 0.35 to 8.12) risk. Patients with CH exhibited a higher risk of vascular access thrombosis (SHR, 2.47; 95% CI, 1.34 to 4.56) and patients with non- DNMT3A CH present with a higher all-cause mortality risk (hazard ratio, 1.71; 95% CI, 1.03 to 2.85). Conclusions Seven percent of patients with ESKD on hemodialysis presented with CH. There was no association between CH and stroke, myocardial infarction, or venous thromboembolism. CH was associated with vascular access thrombosis.