Urothelial protein expression in pediatric patients with ureteropelvic junction obstruction

Ashley R Jackson1,2, Sudipti Gupta1,3, Macie Kercsmar1

  • 1Kidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA.

Insights

Pediatric ureteropelvic junction obstruction (UPJO) shows increased urothelial proteins in urine and obstructed tissue. This suggests urothelial remodeling may protect the kidney in children with UPJO.

Area of Science:

  • Urology
  • Pediatric Nephrology
  • Molecular Biology

Background:

  • Pediatric ureteropelvic junction obstruction (UPJO) is a primary cause of congenital obstructive uropathy.
  • Experimental models suggest urothelial remodeling in UPJO acts as a protective adaptation for kidney integrity.
  • This pilot study investigates urothelial protein expression in human UPJO cases.

Purpose of the Study:

  • To investigate the expression of specific urothelial proteins in urine and resected tissue from children with UPJO.
  • To compare urothelial protein levels between children with UPJO and healthy controls.
  • To explore the localization of these proteins in obstructed urothelium.

Main Methods:

  • Urine samples from children with UPJO and controls were analyzed for urothelial proteins (KRT5, KRT14, KRT20, UPK2, UPK3A) using ELISA, normalized to creatinine.
  • Kidney urine was compared to bladder urine within subjects when available.
  • Immunofluorescence microscopy examined urothelial protein localization in resected kidney pelvises.

Main Results:

  • Urine from children with UPJO exhibited significantly higher levels of KRT14, KRT20, and UPK2 compared to controls.
  • Urothelial protein levels were comparable or higher in urine from the obstructed kidney versus bladder urine.
  • Immunofluorescence revealed specific urothelial cell types expressing KRT14, UPK, and KRT20, with nuclear localization of GRHL3 and PPARγ.

Conclusions:

  • This study provides evidence for elevated urinary urothelial proteins in pediatric UPJO.
  • The findings support the local expression of these proteins by obstructed urothelium in UPJO.
  • Urothelial remodeling is implicated in the protective response to UPJO.
Abstract

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