Acute and chronic glomerular damage is associated with reduced CD133 expression in urinary extracellular vesicles

Am J Physiol Renal Physiol. 2020 Feb 1;318(2):F486-F495. doi: 10.1152/ajprenal.00404.2019. Epub 2019 Dec 23.

Abstract

Extracellular vesicles released into urine (uEVs) can represent interesting biomarkers of renal cell damage. CD133, a stem/progenitor cell marker expressed by renal progenitor cells, is highly expressed in uEVs of healthy individuals. In the present study, we evaluated the level of CD133 in the uEVs of patients with acute and chronic glomerular damage by cytofluorimetric analysis. The level of CD133+ uEVs was significantly decreased in pediatric patients with acute glomerulonephritis during the acute phase of renal damage, while it was restored after the subsequent recovery. A similar decrease was also observed in patients with chronic glomerulonephritis. Moreover, CD133+ uEVs significantly declined in patients with type 2 diabetes, used as validation group, with the lowest levels in patients with albuminuria with diabetic nephropathy. Indeed, receiver-operating characteristic curve analysis indicates the ability of CD133+ uEV values to discriminate the health condition from that of glomerular disease. In parallel, a significant decrease of CD133 in renal progenitor cells and in their derived EVs was observed in vitro after cell treatment with a combination of glucose and albumin overload, mimicking the diabetic condition. These data indicate that the level of CD133+ uEVs may represent an easily accessible marker of renal normal physiology and could provide information on the "reservoir" of regenerating cells within tubules.

Keywords: CD133; extracellular vesicles; prominin; regeneration; renal damage; urine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • AC133 Antigen / urine*
  • Acute Disease
  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Biomarkers / urine
  • Case-Control Studies
  • Cell Proliferation
  • Cells, Cultured
  • Child
  • Child, Preschool
  • Chronic Disease
  • Diabetic Nephropathies / pathology
  • Diabetic Nephropathies / physiopathology
  • Diabetic Nephropathies / urine*
  • Down-Regulation
  • Extracellular Vesicles / metabolism*
  • Extracellular Vesicles / pathology
  • Female
  • Glomerular Filtration Rate
  • Glomerulonephritis / pathology
  • Glomerulonephritis / physiopathology
  • Glomerulonephritis / urine*
  • Humans
  • Kidney Glomerulus / metabolism*
  • Kidney Glomerulus / pathology
  • Kidney Glomerulus / physiopathology
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Prognosis
  • Regeneration
  • Reproducibility of Results
  • Stem Cells / metabolism*
  • Stem Cells / pathology
  • Urinalysis

Substances

  • AC133 Antigen
  • Biomarkers
  • PROM1 protein, human