Novel Lipid Biomarkers of Chronic Kidney Disease of Unknown Etiology Based on Urinary Small Extracellular Vesicles: A Pilot Study of Sugar Cane Workers

Details

• Journal Article:
  Metabolites
• Personal Author:
  Zhou, Jie ; Kroll, Kevin J. ; Butler-Dawson, Jaime ; Krisher, Lyndsay ; Alli, Abdel A. ; Vulpe, Chris ; Denslow, Nancy D.
• Description:
  Background/Objectives: Chronic kidney disease of unknown etiology (CKDu) disproportionately affects young male agricultural workers who are otherwise healthy. There is a scarcity of biomarkers for early detection of this type of kidney disease. We hypothesized that small extracellular vesicles (sEVs) released into urine may provide novel biomarkers. Methods: We obtained two urine samples at the start and the end of a workday in the fields from a limited set of workers with and without kidney impairment. Isolated sEVs were characterized for size, surface marker expression, and purity and, subsequently, their lipid composition was determined by mass spectrometry. Results: The number of particles per ml of urine normalized to osmolality and the size variance were larger in workers with possible CKDu than in control workers. Surface markers CD9, CD63, and CD81 are characteristic of sEVs and a second set of surface markers suggested the kidney as the origin. Differential expression of CD25 and CD45 suggested early inflammation in CKDu workers. Of the twenty-one lipids differentially expressed, several were bioactive, suggesting that they may have essential functions. Remarkably, fourteen of the lipids showed intermediate expression values in sEVs from healthy individuals with acute creatinine increases after a day of work. Conclusions: We identified twenty-one possible lipid biomarkers in sEVs isolated from urine that may be able to distinguish agricultural workers with early onset of CKDu. Differentially expressed surface proteins in these sEVs suggested early-stage inflammation. This pilot study was limited in the number of workers evaluated, but the approach should be further evaluated in a larger population.
• Subjects:
  Agriculture Kidney Occupational Health Safety
• Keywords:
  Agricultural Workers; Lipids; Kidney Damage; Biomarkers; Metabolites; Author Keywords: CKDu; Biomarkers; Lipidomics; Small Extracellular Vesicles
• Source:
  Metabolites 2025 Aug; 15(8):523
• ISSN:
  2218-1989
• Document Type:
  Text
• Funding:
  Cooperative Agreement; Grant
• Genre:
  Journal Article
• Place as Subject:
  Florida ; Colorado ; Atlanta Region [OSHA] ; Birningham Region [OSHA] ; Denver Region [OSHA]
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  18 pdf pages
• Volume:
  15
• Issue:
  8
• NIOSHTIC Number:
  nn:20071360
• Contact Point Address:
  Nancy D. Denslow, Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL 32611, USA
• Email:
  ndenslow@ufl.edu
• Federal Fiscal Year:
  2025
• NORA Priority Area:
  Agriculture, Forestry and Fishing
• Performing Organization:
  University of Florida, Gainesville
• Peer Reviewed:
  True
• Start Date:
  20160930
• End Date:
  20270929
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:36e137d0922112470d163d9a31bebea67cfa27ab8216d9441a39f0636ef66f46122baef309dbe69e6010d2660f2918bee39e2e3314a7a62dde2f7c86956fbb7b
• Download URL:
  https://stacks.cdc.gov/view/cdc/258835/cdc_258835_DS1.pdf
• File Type:
  [PDF - 5.68 MB ]