CHIP and Kidney Outcomes Including Anemia in Patients with CKD

Clonal hematopoiesis of indeterminate potential (CHIP), an inflammatory premalignant disorder related to acquired genetic mutations in hematopoietic stem cells, is common in aging populations. CHIP is known to be associated with cardiovascular morbidity and overall mortality in the general population, but there are few data on its role in chronic kidney disease (CKD).

Caitlyn Viasschaert, MD, MSc, and colleagues conducted a targeted sequencing to detect CHIP mutations in two independent cohorts of 87 and 85 adults with estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m². The researchers also examined kidney function, and hematologic and mineral bone disease parameters cross-sectionally at baseline, and collected creatinine measurements over a 5-year follow-up period. Results were reported online in the Journal of the American Society of Nephrology [doi.org/10.1681/ASN.2021060774].

CHIP was detected in 21% (18/87) and 29% (25/85) of cohort participants at baseline. Among those with CHIP, eGFR was lower and risk of kidney failure as predicted by the Kidney Failure Risk Equation (KFRE) was higher than among those without CHIP. In a Cox proportional hazard model adjusted for age, sex, and baseline eGFR, those with CHIP had a 2.2-fold increased risk of a 50% decline in eGFR or end-stage kidney disease (ESKD) over 5 years of follow-up (hazard ratio, 2.2; 95% confidence interval, 1.2-3.8).

Predictions of ESKD were improved with the addition of CHIP to 2-year and 5-year calibrated KFRE risk models. Those with CHIP also had lower hemoglobin, higher ferritin, and higher red blood cell mean corpuscular volume compared with those without CHIP.

In summary, the researchers said, “In this exploratory analysis of individuals with pre-existing CKD, CHIP was associated with higher baseline KFRE scores, greater progression of CKD, and anemia. Further research is needed to define the nature of the relationship between CHIP and kidney disease progression.”