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We sought to relate urinary IL-9 levels to the release of podocyte-derived extracellular vesicles (EVs) in youth with type 1 diabetes. We related urinary IL-9 levels to clinical variables and studied interactions between urinary IL-9, vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF\u03b1) and interleukin-6 (IL-6) on urinary albumin\/creatinine ratio (ACR) a functional measure of podocyte injury.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We performed an analysis of urine samples and clinical data from a cohort of youth with type 1 diabetes (<jats:italic>n<\/jats:italic>\u2009=\u200953). Cytokines were measured using a Luminex platform (Eve Technologies), and nanoscale flow cytometry was employed to quantify urinary podocyte-derived EVs. All urinary measures were normalized to urinary creatinine.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Mean age was 14.7\u2009\u00b1\u20091.6\u00a0years, and the mean time from diagnosis was 6.7\u2009\u00b1\u20092.9\u00a0years. Mean HbA1c was 70.3\u2009\u00b1\u200913.9\u00a0mmol\/mol, mean ACR was 1.3\u2009\u00b1\u20091.9\u00a0mg\/mmol, and mean eGFR was 140.3\u2009\u00b1\u200932.6\u00a0ml\/min\/1.73\u00a0m<jats:sup>2<\/jats:sup>. IL-9 was inversely related to podocyte EVs (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2212 0.56, <jats:italic>p<\/jats:italic>\u2009=\u20090.003). IL-9 was also inversely related to blood glucose, HbA1C and eGFR (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2212 0.44, <jats:italic>p<\/jats:italic>\u2009=\u20090.002; <jats:italic>r<\/jats:italic>\u2009=\u2009\u2212 0.41, <jats:italic>p<\/jats:italic>\u2009=\u20090.003; <jats:italic>r<\/jats:italic>\u2009=\u2009\u2212\u20090.49, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, respectively) and positively correlated with systolic BP (<jats:italic>r<\/jats:italic>\u2009=\u20090.30, <jats:italic>p<\/jats:italic>\u2009=\u20090.04). There was a significant interaction between IL-9, EVs and ACR (<jats:italic>p<\/jats:italic>\u2009=\u20090.0143), and the relationship between IL-9 and ACR depended on VEGF (<jats:italic>p<\/jats:italic>\u2009=\u20090.0083), TNF\u03b1 (<jats:italic>p<\/jats:italic>\u2009=\u20090.0231) and IL-6 levels (<jats:italic>p<\/jats:italic>\u2009=\u20090.0178).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>IL-9 is associated with podocyte injury in early type 1 diabetes, and there are complex interactions between urinary IL-9, inflammatory cytokines and ACR.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00592-022-01873-4","type":"journal-article","created":{"date-parts":[[2022,4,20]],"date-time":"2022-04-20T20:03:04Z","timestamp":1650484984000},"page":"939-947","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Urinary interleukin-9 in youth with type 1 diabetes mellitus"],"prefix":"10.1007","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2933-2741","authenticated-orcid":false,"given":"Julie","family":"Semenchuk","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2606-733X","authenticated-orcid":false,"given":"Katie","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5506-084X","authenticated-orcid":false,"given":"Rahim","family":"Moineddin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3557-3584","authenticated-orcid":false,"given":"Farid","family":"Mahmud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4718-9408","authenticated-orcid":false,"given":"Allison","family":"Dart","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandy","family":"Wicklow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengxia","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thalia","family":"Medeiros","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5591-2267","authenticated-orcid":false,"given":"James","family":"Scholey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3951-2911","authenticated-orcid":false,"given":"Dylan","family":"Burger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,4,20]]},"reference":[{"issue":"6","key":"1873_CR1","doi-asserted-by":"publisher","first-page":"3283","DOI":"10.4049\/jimmunol.1003049","volume":"186","author":"R Goswami","year":"2011","unstructured":"Goswami R, Kaplan MH (2011) A Brief History of IL-9. 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