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.

不确定潜能克隆造血 (CHIP) 源于突变造血干细胞的克隆扩增。 CHIP 影响 10-20% 的 65 岁以上个体，并与死亡率增加相关，尽管只有一小部分 CHIP 患者进展为明显的血液癌。现在，Caitlyn Vlasschaert 及其同事证明，CHIP 与肾巨噬细胞诱导促炎信号传导以及急性肾损伤 (AKI) 风险增加有关。 “总的来说，我们的研究表明 CHIP 对 AKI 后的恢复具有抑制作用，因为突变的浸润巨噬细胞增加了促炎信号，”他们说。

Vlasschaert 及其同事在三个基于人群的队列（英国生物银行、社区动脉粥样硬化风险队列和心血管健康研究）中首次证明，CHIP 与 AKI 事件风险增加 26% 相关。这种关联在需要透析的患者中更为明显，并且与DNMT3A以外的基因突变相关，包括TET2和JAK2。在两个单独的队列中，非DNMT3A -CHIP 和大型 CHIP 克隆与未解决的 AKI 风险增加超过两倍相关。孟德尔随机化分析支持 CHIP 在 AKI 发病机制中的因果作用。