Clonal Hematopoiesis and Kidney Function in the ASPREE Cohort

Clonal hematopoiesis of indeterminate potential (CHIP) is emerging as a novel risk factor for many nonhematological diseases. Although some studies suggest that CHIP is associated with adverse kidney outcomes, the results are conflicting across cohorts.

In this secondary analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) trial, we assessed the association between CHIP and kidney function in 9434 community-dwelling adults aged > 70 years. At baseline, participants were free of cardiovascular disease (CVD) and major life-limiting illness. In addition, we performed meta-analysis of published cohorts investigating the association between CHIP and incident kidney function decline.

Of the participants, 2124 of 9434 (22.5%) had CHIP, of whom 532 had variant allele fraction (VAF) ≥ 10% and 887 had a single non-DNMT3A mutation. After adjusting for age and other confounders, there was no association between CHIP, including large CHIP or non-DNMT3A CHIP, and baseline estimated glomerular filtration rate (eGFR), baseline log-transformed urinary albumin-to-creatinine ratio (UACR), or rate of change of eGFR or log(UACR) over a median of 8.4 years of follow-up. Incident kidney function decline was not increased in this cohort, including in those with non-DNMT3A CHIP. Meta-analysis with other published cohorts supports an increased risk of incident kidney function decline in those with non-DNMT3A CHIP, with considerable heterogeneity.

We propose that the effect of CHIP is modified by participant factors, including comorbidities, partly accounting for heterogeneity across cohorts. This work contributes to a growing understanding of the interplay between CHIP and disease, and considerations in translating findings from large observational studies to individuals with CHIP.