Clonal haematopoiesis of indeterminate potential (CHIP) arises from the clonal expansion of a mutated haematopoietic stem cell. CHIP affects 10–20% of individuals aged ≥65 years and is associated with increased mortality, although only a small proportion of patients with CHIP progress to overt haematological cancer. Now, Caitlyn Vlasschaert and colleagues demonstrate that CHIP is associated with the induction of proinflammatory signalling by renal macrophages and an increased risk of acute kidney injury (AKI). “Overall, our study suggests that CHIP has an inhibitory role in recovery after AKI because of increased proinflammatory signalling by mutated infiltrating macrophages,” they say.

Across three population-based cohorts (the UK Biobank, the Atherosclerosis Risk in Communities cohort and the Cardiovascular Health Study), Vlasschaert and colleagues first demonstrate that CHIP is associated with a 26% higher risk of incident AKI. This association was more pronounced in patients requiring dialysis and was associated with mutations in genes other than DNMT3A, including TET2 and JAK2. In two separate cohorts, non-DNMT3A-CHIP and large CHIP clones were associated with a greater than two-fold increased risk of non-resolving AKI. Mendelian randomization analyses supported a causal role for CHIP in AKI pathogenesis.