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Background <p>Pediatric ureteropelvic junction obstruction (UPJO) is the leading cause of congenital obstructive uropathy. Experimental models have identified local urothelial remodeling in UPJO and implicated this remodeling as a protective adaptation to preserve kidney structural integrity and function. We investigated the expression of urothelial proteins in human urine and resected tissue specimens from children with UPJO in a pilot study.</p> Methods <p>Children undergoing pyeloplasty for clinically significant UPJO and healthy age- and sex-matched controls were included. Bladder urine samples were evaluated by ELISA for urothelial proteins (KRT5, KRT14, KRT20, UPK2, UPK3A) and normalized to creatinine (Cr). When available, kidney urine collected at pyeloplasty was compared to bladder urine from the same subject. Urothelial proteins were localized by immunofluorescence microscopy in surgically resected kidney pelvises proximal to the obstruction.</p> Results <p>Twenty-three UPJO and 14 control urines were evaluated. KRT14/Cr, KRT20/Cr, and UPK2/Cr levels were significantly higher in UPJO urine compared to controls (<i>p</i> &lt; 0.05; Mann–Whitney <i>U</i> test). Levels of urothelial proteins were as high or higher in urine obtained from the obstructed kidney when compared to paired bladder urine. Immunofluorescence microscopy of obstructed urothelium identified basal KRT14+ cells, pan-urothelial UPK+ cells, and superficial KRT20 + cells, with nuclear localization of two transcription factors implicated in obstructive urothelial remodeling, GRHL3 and PPARγ.</p> Conclusions <p>We provide evidence of increased urothelial proteins in urine from children with UPJO in this pilot study, along with evidence of their local expression by obstructed urothelium.</p> Graphical abstract <p></p>

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Urothelial protein expression in pediatric patients with ureteropelvic junction obstruction

  • 期刊论文

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  • 发表日期：

    2026年7月10日

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  • Ashley R. Jackson,
  • Sudipti Gupta,
  • Macie Kercsmar,
  • John W. Froehlich,
  • Richard S. Lee,
  • Brian Becknell,
  • Christina B. Ching

摘要

Background

Pediatric ureteropelvic junction obstruction (UPJO) is the leading cause of congenital obstructive uropathy. Experimental models have identified local urothelial remodeling in UPJO and implicated this remodeling as a protective adaptation to preserve kidney structural integrity and function. We investigated the expression of urothelial proteins in human urine and resected tissue specimens from children with UPJO in a pilot study.

Methods

Children undergoing pyeloplasty for clinically significant UPJO and healthy age- and sex-matched controls were included. Bladder urine samples were evaluated by ELISA for urothelial proteins (KRT5, KRT14, KRT20, UPK2, UPK3A) and normalized to creatinine (Cr). When available, kidney urine collected at pyeloplasty was compared to bladder urine from the same subject. Urothelial proteins were localized by immunofluorescence microscopy in surgically resected kidney pelvises proximal to the obstruction.

Results

Twenty-three UPJO and 14 control urines were evaluated. KRT14/Cr, KRT20/Cr, and UPK2/Cr levels were significantly higher in UPJO urine compared to controls (p < 0.05; Mann–Whitney U test). Levels of urothelial proteins were as high or higher in urine obtained from the obstructed kidney when compared to paired bladder urine. Immunofluorescence microscopy of obstructed urothelium identified basal KRT14+ cells, pan-urothelial UPK+ cells, and superficial KRT20 + cells, with nuclear localization of two transcription factors implicated in obstructive urothelial remodeling, GRHL3 and PPARγ.

Conclusions

We provide evidence of increased urothelial proteins in urine from children with UPJO in this pilot study, along with evidence of their local expression by obstructed urothelium.

Graphical abstract