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

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 the uEVs of healthy subjects. We here 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 paediatric acute glomerulonephritis patients during the acute phase of renal damage, while it was restored after the subsequent recovery. A similar decrease was also observed in chronic glomerulonephritis patients. Moreover, CD133 + uEVs significantly declined in type 2 diabetic patients, used as validation group, with lowest levels in albuminuric patients with diabetic nephropathy. Indeed, ROC 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 "reservoire" of regenerating cells within tubules.

Urinary extracellular vesicles: A position paper by the Urine Task Force of the International Society for Extracellular Vesicles

“…Recently, a bead‐based commercial kit detected up to 37 surface markers of EVs captured by CD63, CD9, and CD81‐coated beads (Wiklander et al., 2018). For uEVs, CD24, and CD133 might be of interest as markers of kidney function whereas other markers may identify kidney infiltrating cells (Dimuccio et al., 2020). Numerous omics analyses have also been performed to define the molecular content of uEVs and identify novel biomarkers for several diseases.…”

Urinary Extracellular Vesicles for Diabetic Kidney Disease Diagnosis

“…The numbers of CD133+uEVs decreased gradually as DKD progresses according to micro- or macroalbuminuria. Moreover, the ability of CD133+uEVs to discriminate the healthy condition from that of glomerular disease was corroborated by ROC curves [ 85 ]. In vitro, albumin reduced the content of the CD133 marker in renal progenitor cell-derived EVs, which was further decreased by the coincubation with both, albumin and HG [ 85 ].…”

Extracellular vesicles mediate cellular interactions in renal diseases—Novel views of intercellular communications in the kidney

“…Importantly, elevated levels of CD133 + EVs have been reported in patients receiving renal transplantation, indicating that CD133 + EVs may be important for maintaining the homeostatic status of the kidney (Dimuccio et al, 2014). Compared to healthy individuals, pediatric patients with acute glomerulonephritis have shown a reduced urinary level of CD133 + EVs, which return to normal levels with recovery from the renal disease (Dimuccio et al, 2020). This study suggests that urinary levels of CD133 + EVs may serve as a biomarker for monitoring the renal disease activity.…”