Plasminogenuria Is Associated with Podocyte Injury, Edema, and Kidney Dysfunction in Incident Glomerular Disease

Details

• Personal Author:
  Anandakrishnan N ; Azeloglu EU ; Bagiella E ; Campbell KN ; Chauhan K ; Coca SG ; Egerman MA ; Li H ; Meliambro K ; Mosoyan G ; Raij L ; Reyes-Bahamonde J ; Runxia T ; Salem F ; Wong JS ; Wong NJ
• Description:
  Urinary plasminogen/plasmin, or plasmin (ogen) uria, has been demonstrated in proteinuric patients and exposure of cultured podocytes to plasminogen results in injury via oxidative stress pathways. A causative role for plasmin (ogen) as a "second hit" in kidney disease progression has yet to have been demonstrated in vivo. Additionally, association between plasmin (ogen) uria and kidney function in glomerular diseases remains unclear. We performed comparative studies in a puromycin aminonucleoside (PAN) nephropathy rat model treated with amiloride, an inhibitor of plasminogen activation, and measured changes in plasmin (ogen) uria. In a glomerular disease biorepository cohort (n = 128), we measured time-of-biopsy albuminuria, proteinuria, and plasmin (ogen) uria for correlations with kidney outcomes. In cultured human podocytes, plasminogen treatment was associated with decreased focal adhesion marker expression with rescue by amiloride. Increased glomerular plasmin (ogen) was found in PAN rats and focal segmental glomerulosclerosis (FSGS) patients. PAN nephropathy was associated with increases in plasmin (ogen) uria and proteinuria. Amiloride was protective against PAN-induced glomerular injury, reducing CD36 scavenger receptor expression and oxidative stress. In patients, we found associations between plasmin (ogen) uria and edema status as well as eGFR. Our study demonstrates a role for plasmin (ogen)-induced podocyte injury in the PAN nephropathy model, with amiloride having podocyte-protective properties. In one of the largest glomerular disease cohorts to study plasminogen, we validated previous findings while suggesting a potentially novel relationship between plasmin (ogen) uria and estimated glomerular filtration rate (eGFR). Together, these findings suggest a role for plasmin (ogen) in mediating glomerular injury and as a viable targetable biomarker for podocyte-sparing treatments. [Description provided by NIOSH]
• Subjects:
  Albumins Anti-Bacterial Agents Biomarkers Blood Nervous System Occupational Health Safety Urine
• Keywords:
  Albumin Amino Groups Antibiotics Author Keywords: Amiloride Blood Vessels Edema EGFR Glomerular Kidney Cells Kidney Damage Kidney Disorders Kidney Function Nerve Fibers Nucleosides Oxidative Stress Plasminogen Podocytes Potassium Proteins Urine Chemistry

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• ISSN:
  0892-6638
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Florida ; New Jersey ; New York ; OSHA Region 2 ; OSHA Region 4
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  34
• Issue:
  12
• NIOSHTIC Number:
  nn:20061233
• Citation:
  FASEB J 2020 Dec; 34(12):16191-16204
• Contact Point Address:
  Kirk N. Campbell, Division of Nephrology, Department of Medicine, Icahn School of Medicine at Mount Sinai, 1 Gustave Levy Place, Box 1243, New York, NY, USA
• Email:
  kirk.campbell@mssm.edu
• CAS Registry Number:
  Aminonucleoside (CAS RN 58-60-6)
• Federal Fiscal Year:
  2021
• Performing Organization:
  Icahn School of Medicine at Mount Sinai, New York
• Peer Reviewed:
  True
• Start Date:
  20170701
• Source Full Name:
  The FASEB Journal
• End Date:
  20200630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:10d693a8c20ca5984fa2dccecfad0ae9b974fdfdcd77060a10358a77b52ca32ef0025f9ababbf36a4aea2402846b4c088dc653f711123c738e5cce846c364d34
• Download URL:
  https://stacks.cdc.gov/view/cdc/224838/cdc_224838_DS1.pdf
• File Type:
  [PDF - 4.25 MB ]