Yu Zhi, Vlasschaert Caitlyn, Natarajan Pradeep
Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
J Am Soc Nephrol. 2025 Apr 15. doi: 10.1681/ASN.0000000739.
Chronic kidney disease (CKD) afflicts over 10% of US adults, with its prevalence increasing sharply with age. Clonal hematopoiesis of indeterminate potential (CHIP) is a common, genetically heterogeneous blood cell disorder characterized by the age-related clonal expansion of hematopoietic cells driven by leukemogenic somatic mutations yet without hematologic malignancy or dysplasia. While CHIP is a strong risk factor for future hematologic malignancy (estimated at ∼0.5% per year, compared to <0.1% for those without CHIP), it is also linked to twofold higher cardiovascular disease in epidemiologic, cell-based, and murine studies. However, more recent work has implicated CHIP with renal outcomes such as chronic kidney disease as well as acute kidney injury, independent of traditional risk factors. This review covers the observations and proposed hypotheses linking CHIP and kidney disease. The review also underscores the need for further research to elucidate the distinct pathways through which CHIP may contribute to CKD and its comorbidities, considering the heterogeneity within CKD stages and etiologies, as well as whether CHIP is a causal driver of kidney disease or a marker of aging and comorbidity. Finally, we discuss the potential of anti-inflammatory treatments to mitigate CHIP's adverse effects on kidney health, aiming to improve management strategies for patients with CHIP-associated kidney diseases.
慢性肾脏病（CKD）影响着超过10%的美国成年人，其患病率随年龄急剧上升。不确定潜能克隆造血（CHIP）是一种常见的、基因异质性的血细胞疾病，其特征是由致白血病体细胞突变驱动的造血细胞随年龄增长而克隆性扩增，但无血液系统恶性肿瘤或发育异常。虽然CHIP是未来血液系统恶性肿瘤的一个强风险因素（估计每年约0.5%，而无CHIP者<0.1%），但在流行病学、细胞研究和小鼠研究中，它也与心血管疾病风险增加两倍有关。然而，最近的研究表明，CHIP与慢性肾脏病以及急性肾损伤等肾脏结局有关，且独立于传统风险因素。本综述涵盖了将CHIP与肾脏疾病联系起来的观察结果和提出的假设。该综述还强调，鉴于CKD阶段和病因的异质性，以及CHIP是肾脏疾病的因果驱动因素还是衰老和合并症的标志物，需要进一步研究以阐明CHIP可能导致CKD及其合并症的不同途径。最后，我们讨论了抗炎治疗减轻CHIP对肾脏健康不良影响的潜力，旨在改善CHIP相关肾脏疾病患者的管理策略。
