Clonal hematopoiesis of indeterminate potential is associated with worse kidney function and anemia in a cohort of patients with advanced chronic kidney disease

Abstract

AbstractBackgroundClonal hematopoiesis of indeterminate potential (CHIP) is an inflammatory premalignant disorder resulting from acquired genetic mutations in hematopoietic stem cells. CHIP is common in aging populations and associated with cardiovascular morbidity and overall mortality, but its role in chronic kidney disease (CKD) has not been investigated.MethodsWe performed targeted sequencing to detect CHIP mutations in a cohort of 87 adults with eGFR < 60 ml/min/1.73m2. Kidney function, hematologic, and mineral bone disease parameters were assessed cross-sectionally at baseline, and a total of 2,091 creatinine measurements and 3,382 hemoglobin measurements were retrospectively collected over the following 12-year period.ResultsAt baseline, 20 of 87 (23%) cohort participants had CHIP detected. Those with CHIP had lower baseline eGFR (22.3 ± 11.2 vs. 28.2 ± 11.5 ml/min/1.73 m2, P = 0.04) in age- and sex-adjusted regression models. Individuals with CHIP had a 2.5–fold increased risk of incident 50% decline in eGFR or ESKD in a Cox proportional hazard model adjusted for age and sex (95% confidence interval, 1.3–4.7). The annualized rate of eGFR decline adjusted for age and sex was -2.3 ±1.1 ml/min/1.73m2 per year in those with CHIP versus -1.6 ±0.5 ml/min/1.73m2 per year in those without CHIP. Further, those with CHIP had lower hemoglobin at baseline (11.6 ± 0.3 vs. 12.8 ± 0.2 g/dL, P = 0.0003) and throughout the follow-up period despite a greater use of erythropoiesis-stimulating agents.ConclusionIn those with pre-existing CKD, CHIP was associated with lower eGFR at baseline, faster progression of CKD, and anemia.