We sought to determine the relationship between age-related clonal hematopoiesis (CH) and chronic kidney disease (CKD). CH, defined as mosaic chromosome abnormalities (mCA) and/or driver mutations was identified in 5449 (2.9%) eligible UK Biobank participants (n = 190,487 median age = 58 years). CH was negatively associated with glomerular filtration rate estimated from cystatin-C (eGFR.cys; β = −0.75, P = 2.37 × 10^–4), but not with eGFR estimated from creatinine, and was specifically associated with CKD defined by eGFR.cys < 60 (OR = 1.02, P = 8.44 × 10^–8). In participants without prevalent myeloid neoplasms, eGFR.cys was associated with myeloid mCA (n = 148, β = −3.36, P = 0.01) and somatic driver mutations (n = 3241, β = −1.08, P = 6.25 × 10^–5) associated with myeloid neoplasia (myeloid CH), specifically mutations in CBL, TET2, JAK2, PPM1D and GNB1 but not DNMT3A or ASXL1. In participants with no history of cardiovascular disease or myeloid neoplasms, myeloid CH increased the risk of adverse outcomes in CKD (HR = 1.6, P = 0.002) compared to those without myeloid CH. Mendelian randomisation analysis provided suggestive evidence for a causal relationship between CH and CKD (P = 0.03). We conclude that CH, and specifically myeloid CH, is associated with CKD defined by eGFR.cys. Myeloid CH promotes adverse outcomes in CKD, highlighting the importance of the interaction between intrinsic and extrinsic factors to define the health risk associated with CH.

我们试图确定与年龄相关的克隆性造血 (CH) 和慢性肾病 (CKD) 之间的关系。CH，定义为镶嵌染色体异常 (mCA) 和/或驱动突变，在 5449 名 (2.9%) 符合条件的英国生物库参与者中发现 ( n  = 190,487 中位年龄 = 58 岁)。CH 与根据 cystatin-C 估算的肾小球滤过率呈负相关（eGFR.cys；β  = -0.75，P  = 2.37 × ^10-4），但与根据肌酐估算的 eGFR 无关，并且与 eGFR 定义的 CKD 明确相关。 cys < 60 (OR = 1.02, P  = 8.44 × 10 ^–8 )。在没有普遍髓系肿瘤的参与者中，eGFR.cys 与髓系 mCA 相关（n = 148, β  = -3.36, P  = 0.01) 和体细胞驱动突变 ( n  = 3241, β  = -1.08, P  = 6.25 × 10 ^–5 ) 与髓样肿瘤 (myeloid CH) 相关，特别是CBL、TET2、JAK2、PPM1D和GNB1但不是DNMT3A或ASXL1。在没有心血管疾病或髓系肿瘤病史的参与者中，髓系 CH 增加了 CKD 不良结局的风险（HR = 1.6，P = 0.002) 与没有骨髓 CH 的人相比。孟德尔随机化分析为 CH 和 CKD 之间的因果关系提供了暗示性证据（P  = 0.03）。我们得出结论，CH，特别是骨髓 CH，与 eGFR.cys 定义的 CKD 相关。髓系 CH 促进 CKD 的不良后果，突出了内在和外在因素之间相互作用的重要性，以确定与 CH 相关的健康风险。