Urinary EGF and MCP-1 and Risk of CKD After Cardiac Surgery

Details

• Personal Author:
  Bomback AS ; Coca SG ; Garg AX ; Jia Y ; Ju W ; Kellum JA ; Koyner JL ; Kretzler M ; Mansour SG ; McArthur E ; Menez S ; Menon R ; Moledina DG ; Obeid W ; Parikh CR ; Shlipak MG ; Thiessen Philbrook H ; Translational Research Investigating Biomarker Endpoints in AKI (TRIBE-AKI) Consortium and the Kidney Precision Medicine Project
• Description:
  BACKGROUND. Assessment 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. METHODS. We 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. RESULTS. Over 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. CONCLUSION. Urinary 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. [Description provided by NIOSH]
• Subjects:
  Biomarkers Cardiovascular System Chronic Disease Occupational Health Safety
• Keywords:
  Cardiology Chronic Diseases Gene Expression Kidney Disorders Kidneys Nephrological Disorders Surgery
• ISSN:
  2379-3708
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  California ; Connecticut ; Illinois ; Maryland ; Michigan ; New York ; OSHA Region 1 ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 5 ; OSHA Region 9 ; Pennsylvania
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  6
• Issue:
  11
• NIOSHTIC Number:
  nn:20063292
• Citation:
  JCI Insight 2021 Jun; 6(11):e147464
• Contact Point Address:
  Chirag R. Parikh, Division of Nephrology, Johns Hopkins University School of Medicine, 1830 E Monument St, Ste 416, Baltimore, Maryland 21287, USA
• Email:
  chirag.parikh@jhmi.edu
• Federal Fiscal Year:
  2021
• Performing Organization:
  Icahn School of Medicine at Mount Sinai, New York
• Peer Reviewed:
  True
• Start Date:
  20170701
• Source Full Name:
  JCI Insight
• End Date:
  20200630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f061b1cffd133fae33cee84d80b6d86e277986e655b4ea685a8d1ea9a9aa9bcfe69b8a43aa8296049a2fa0e81ef6ca258723dac9f22e1049d447a99737d32579
• Download URL:
  https://stacks.cdc.gov/view/cdc/226380/cdc_226380_DS1.pdf
• File Type:
  [PDF - 1.78 MB ]