Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Division of Nephrology, Department of Medicine, and Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.
JCI Insight. 2021 Jun 8;6(11):147464. doi: 10.1172/jci.insight.147464.
BACKGROUNDAssessment of chronic kidney disease (CKD) risk after acute kidney injury (AKI) is based on limited markers primarily reflecting glomerular function. We evaluated markers of cell integrity (EGF) and inflammation (monocyte chemoattractant protein-1, MCP-1) for predicting long-term kidney outcomes after cardiac surgery.METHODSWe measured EGF and MCP-1 in postoperative urine samples from 865 adults who underwent cardiac surgery at 2 sites in Canada and the United States and assessed EGF and MCP-1's associations with the composite outcome of CKD incidence or progression. We used single-cell RNA-Seq (scRNA-Seq) of AKI patient biopsies to perform transcriptomic analysis of programs corregulated with the associated genes.RESULTSOver a median (IQR) follow-up of 5.8 (4.2-7.1) years, 266 (30.8%) patients developed the composite CKD outcome. Postoperatively, higher levels of urinary EGF were protective and higher levels of MCP-1 were associated with the composite CKD outcome (adjusted HR 0.83, 95% CI 0.73-0.95 and 1.10, 95% CI 1.00-1.21, respectively). Intrarenal scRNA-Seq transcriptomes in patients with AKI-defined cell populations revealed concordant changes in EGF and MCP-1 levels and underlying molecular processes associated with loss of EGF expression and gain of CCL2 (encoding MCP-1) expression.CONCLUSIONUrinary EGF and MCP-1 were each independently associated with CKD after cardiac surgery. These markers may serve as noninvasive indicators of tubular damage, supported by tissue transcriptomes, and provide an opportunity for novel interventions in cardiac surgery.TRIAL REGISTRATIONClinicalTrials.gov NCT00774137.FUNDINGThe NIH funded the TRIBE-AKI Consortium and Kidney Precision Medicine Project. Yale O'Brien Kidney Center, American Heart Association, Patterson Trust Fund, Dr. Adam Linton Chair in Kidney Health Analytics, Canadian Institutes of Health Research, ICES, Ontario Ministry of Health and Long-Term Care, Academic Medical Organization of Southwestern Ontario, Schulich School of Medicine & Dentistry, Western University, Lawson Health Research Institute, Chan Zuckerberg Initiative Human Cell Atlas Kidney Seed Network.
急性肾损伤 (AKI) 后慢性肾脏病 (CKD) 风险的评估主要基于反映肾小球功能的有限标志物。我们评估了细胞完整性标志物（表皮生长因子，EGF）和炎症标志物（单核细胞趋化蛋白-1，MCP-1），以预测心脏手术后的长期肾脏结局。
我们测量了加拿大和美国两个地点进行心脏手术的 865 名成年人术后尿液样本中的 EGF 和 MCP-1，并评估了 EGF 和 MCP-1 与 CKD 发生率或进展的复合结局之间的关联。我们使用 AKI 患者活检的单细胞 RNA-Seq(scRNA-Seq) 对相关基因的相关基因进行了转录组分析。
在中位数（IQR）为 5.8（4.2-7.1）年的随访中，266（30.8%）名患者发生了复合 CKD 结局。术后，尿液 EGF 水平升高具有保护作用，而 MCP-1 水平升高与复合 CKD 结局相关（调整后的 HR 分别为 0.83，95%CI 0.73-0.95 和 1.10，95%CI 1.00-1.21）。AKI 定义的细胞群患者的肾内 scRNA-Seq 转录组显示 EGF 和 MCP-1 水平以及与 EGF 表达丧失和 CCL2（编码 MCP-1）表达增加相关的潜在分子过程的一致性变化。
尿液 EGF 和 MCP-1 均与心脏手术后的 CKD 独立相关。这些标志物可能是肾小管损伤的非侵入性指标，得到组织转录组的支持，并为心脏手术中的新干预措施提供了机会。
ClinicalTrials.gov NCT00774137。
美国国立卫生研究院资助了 TRIBE-AKI 联盟和肾脏精准医学项目。耶鲁奥布赖恩肾脏中心、美国心脏协会、帕特森信托基金、肾脏健康分析亚当林顿主席、加拿大卫生研究院、ICES、安大略省卫生部和长期护理部、西南安大略省学术医疗组织、舒立克医学院和牙科学院、西部大学、劳森健康研究所、Chan Zuckerberg 倡议人类细胞图谱肾脏种子网络。
