ArticleFrontiers in cell and developmental biology2026
Defining the urine proteome in boys with posterior urethral valves: a pilot study.
Article in Frontiers in cell and developmental biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Introduction: Posterior urethral valves (PUV) is the most common cause of congenital bladder outlet obstruction and a major etiology of end-stage kidney disease in boys. There are significant knowledge gaps about the pathogenesis and prognostic indicators of kidney and bladder dysfunction in boys with PUV. Methods: We utilized liquid chromatography-tandem mass spectrometry to analyze the urine proteome in a pilot cohort of 20 boys with PUV compared to 20 unaffected controls, with a focus on estimated glomerular filtration rate (eGFR) variation within the PUV group and its impact on urine protein signatures. Eight complementary workflows for differential expression analysis were developed to ensure robust detection of differential protein expression. A single-cell RNA-seq atlas of 162,083 healthy kidney, ureter, and bladder cells was assembled to infer tissue and cellular origins of PUV-associated proteins. Results: In cases of PUV with preserved eGFR, upregulation of keratins and uroplakins was detected, suggestive of urothelial injury and remodeling that may reflect bladder dysfunction that occurs early in the disease process, even before a decline in renal function. In contrast, cases with low eGFR were associated with declining levels of the proteins related to viability and synthetic function of specific nephron and collecting duct segments, along with increased levels of proteins related to complement activation and inflammation, suggestive of progressive renal injury. The single-cell atlas provided biological context, identifying putative renal and urothelial cell sources for these proteins. Conclusion: This integrative analysis highlights biological pathways and proteins that may reflect kidney and urinary tract injury and dysfunction in a pilot cohort of boys with PUV. These initial findings warrant further testing in longitudinal studies with larger cohorts to link the urine proteome to clinically relevant kidney and bladder outcomes.
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