{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T06:15:36Z","timestamp":1778652936633,"version":"3.51.4"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcell.2026.1752740","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:55:29Z","timestamp":1778651729000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Defining the urine proteome in boys with posterior urethral valves: a pilot study"],"prefix":"10.3389","volume":"14","author":[{"given":"Xin","family":"Wang","sequence":"first","affiliation":[{"name":"Kidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children\u2019s","place":["Columbus, OH, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanna","family":"Cortado","sequence":"additional","affiliation":[{"name":"Kidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children\u2019s","place":["Columbus, OH, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liwen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Mass Spectrometry and Proteomics Facility, Comprehensive Cancer Center, The Ohio State University","place":["Columbus, OH, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina B.","family":"Ching","sequence":"additional","affiliation":[{"name":"Kidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children\u2019s","place":["Columbus, OH, United States"]},{"name":"Department of Urology, Nationwide Children\u2019s Hospital","place":["Columbus, OH, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley R.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Kidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children\u2019s","place":["Columbus, OH, United States"]},{"name":"Division of Nephrology and Hypertension, Nationwide Children\u2019s Hospital","place":["Columbus, OH, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John W.","family":"Froehlich","sequence":"additional","affiliation":[{"name":"Department of Urology, Boston Children\u2019s Hospital","place":["Boston, MA, United States"]},{"name":"Department of Surgery, Harvard Medical School","place":["Boston, MA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard S.","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Urology, Boston Children\u2019s Hospital","place":["Boston, MA, United States"]},{"name":"Department of Surgery, Harvard Medical School","place":["Boston, MA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Becknell","sequence":"additional","affiliation":[{"name":"Kidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children\u2019s","place":["Columbus, OH, United States"]},{"name":"Division of Nephrology and Hypertension, Nationwide Children\u2019s Hospital","place":["Columbus, OH, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daryl","family":"McLeod","sequence":"additional","affiliation":[{"name":"Kidney and Urinary Tract Center, The Abigail Wexner Research Institute at Nationwide Children\u2019s","place":["Columbus, OH, United States"]},{"name":"Department of Urology, Nationwide Children\u2019s Hospital","place":["Columbus, OH, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"661496","DOI":"10.1101\/661496","article-title":"proDA: probabilistic dropout analysis for identifying differentially abundant proteins in label-free mass spectrometry","author":"Ahlmann-Eltze","year":"2019","journal-title":"Biorxiv."},{"key":"B2","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.tjem.2018.08.001","article-title":"User's guide to correlation coefficients","volume":"18","author":"Akoglu","year":"2018","journal-title":"Turkish Journal Emergency Medicine"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e14242","DOI":"10.14814\/phy2.14242","article-title":"Urinary angiotensinogen antedates the development of stage 3 CKD in patients with type 1 diabetes mellitus","volume":"7","author":"Ba Aqeel","year":"2019","journal-title":"Physiol. 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