Department of Medicine, Queen's University, Kingston, Ontario, Canada.
Department of Pathology and Molecular Medicine, Queen's University, Kingston, Ontario, Canada.
J Am Soc Nephrol. 2022 May;33(5):985-995. doi: 10.1681/ASN.2021060774. Epub 2022 Feb 23.
Clonal hematopoiesis of indeterminate potential (CHIP) is an inflammatory premalignant disorder resulting from acquired genetic mutations in hematopoietic stem cells. This condition is common in aging populations and associated with cardiovascular morbidity and overall mortality, but its role in CKD is unknown.
We performed targeted sequencing to detect CHIP mutations in two independent cohorts of 87 and 85 adults with an eGFR<60 ml/min per 1.73m. We also assessed kidney function, hematologic, and mineral bone disease parameters cross-sectionally at baseline, and collected creatinine measurements over the following 5-year period.
At baseline, CHIP was detected in 18 of 87 (21%) and 25 of 85 (29%) cohort participants. Participants with CHIP were at higher risk of kidney failure, as predicted by the Kidney Failure Risk Equation (KFRE), compared with those without CHIP. Individuals with CHIP manifested a 2.2-fold increased risk of a 50% decline in eGFR or ESKD over 5 years of follow-up (hazard ratio 2.2; 95% confidence interval, 1.2 to 3.8) in a Cox proportional hazard model adjusted for age, sex, and baseline eGFR. The addition of CHIP to 2-year and 5-year calibrated KFRE risk models improved ESKD predictions. Those with CHIP also had lower hemoglobin, higher ferritin, and higher red blood cell mean corpuscular volume versus those without CHIP.
In this exploratory analysis of individuals with preexisting CKD, CHIP was associated with higher baseline KFRE scores, greater progression of CKD, and anemia. Further research is needed to define the nature of the relationship between CHIP and kidney disease progression.
不确定潜能的克隆性造血（CHIP）是一种炎症性癌前异常，由造血干细胞获得性基因突变引起。这种情况在老年人群中很常见，与心血管发病率和总体死亡率相关，但在 CKD 中的作用尚不清楚。
我们在两个独立的队列中对 87 名和 85 名 eGFR<60 ml/min per 1.73m 的成年人进行了靶向测序，以检测 CHIP 突变。我们还在基线时进行了横断面的肾脏功能、血液学和矿物质骨骼疾病参数评估，并在接下来的 5 年期间收集了肌酐测量值。
基线时，87 名队列参与者中有 18 名（21%）和 85 名队列参与者中有 25 名（29%）检测到 CHIP。与无 CHIP 者相比，CHIP 患者的肾脏衰竭风险更高，这与肾衰竭风险方程（KFRE）的预测一致。在调整年龄、性别和基线 eGFR 的 Cox 比例风险模型中，CHIP 患者在 5 年随访期间 eGFR 下降 50%或进入终末期肾病的风险增加 2.2 倍（风险比 2.2；95%置信区间，1.2 至 3.8）。在 2 年和 5 年校准的 KFRE 风险模型中加入 CHIP 可改善 ESKD 预测。与无 CHIP 者相比，CHIP 患者的血红蛋白水平更低，铁蛋白水平更高，红细胞平均体积更大。
在这项对预先存在 CKD 的个体的探索性分析中，CHIP 与更高的基线 KFRE 评分、CKD 进展更快以及贫血有关。需要进一步研究来确定 CHIP 与肾脏疾病进展之间的关系性质。
