Association of Clonal Hematopoiesis of Indeterminate… : Journal of the American Society of Nephrology
HIP is greater for somatic mutations in pre-defined CHIP driver genes other than DNMT3A (referred to as non-DNMT3A CHIP). We sought to assess the prospective association between CHIP and cardiovascular events in patients with CKD. Methods: CHIP was measured by high-depth targeted sequencing. The primary analysis tested the association of somatic mutations in non-DNMT3A CHIP driver genes with a composite cardiovascular disease endpoint of myocardial infarction, stroke, congestive heart failure, and peripheral artery disease in 5,043 patients with CKD in four prospective cohorts. Sensitivity analyses examined the effect of CHIP subtypes, race, baseline comorbidities, APOL1 risk alleles, and IL6R p.Asp358Ala genotype. Results: At baseline, patients had a mean age of 66 ± 12 years and eGFR of 43 ± 18 ml/min/1.73m2. CHIP was present in 24% of patients, with 13% of all patients carrying acquired non-DNMT3A mutations. Non-DNMT3A CHIP was associated with a 36% higher risk of the composite card
