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Transl. Med."],"published-print":{"date-parts":[[2026,1,14]]},"abstract":"<jats:p>\n                    Idiopathic nephrotic syndrome (INS) is a podocyte disease triggered by immune-derived factors. Endothelial activation occurs in this context, but whether the activated endothelium contributes to podocyte injury is unknown. We tested the hypothesis that CD93, a protein primarily expressed in the endothelium, is a contributory factor of podocyte injury. We studied 460 patients with INS and 150 with other podocytopathies. CD93 was analyzed in kidney tissue, urine, and serum samples. We tested the efficacy of CD93 blockade in vitro and in vivo and investigated the relationship between soluble CD93 and clinical outcomes in human INS. CD93 was highly expressed by glomerular endothelial cells (GEnCs) in human INS, and INS sera stimulated cultured human GEnCs to release CD93. Mechanistically, soluble CD93 mediated podocyte activation via \u03b21 integrin\/FAK signaling in cultured human podocytes. CD93 blockade mitigated the activation of cultured human podocytes and albumin permeability in human GEnC-podocyte cocultures as well as albuminuria, glomerulosclerosis, and podocyte loss in two models of nephrotic syndrome: podocyte-specific transforming growth factor\u2013\u03b21 signaling (\n                    <jats:italic toggle=\"yes\">PodTgfbr1<\/jats:italic>\n                    ) mice and adriamycin-treated mice.\n                    <jats:italic toggle=\"yes\">Cd93<\/jats:italic>\n                    knockout mice showed less proteinuria and glomerulosclerosis, compared with controls, after adriamycin injection. In patients with INS, soluble CD93 was high in urine in ~90% and 50% of patients in relapse and remission, respectively. High urinary CD93 was associated with faster decline in kidney function and slower response to immunosuppression. Soluble and glomerular CD93 was also elevated in other podocytopathies. We conclude that soluble CD93 contributes to podocyte injury.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adw2206","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T18:58:13Z","timestamp":1768417093000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":4,"title":["Endothelial cell\u2013released CD93 contributes to podocyte injury in idiopathic nephrotic syndrome"],"prefix":"10.1126","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3745-9603","authenticated-orcid":true,"given":"Colin","family":"Bauer","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Section of Pediatric Nephrology, Children\u2019s Hospital Colorado, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3338-1172","authenticated-orcid":true,"given":"Federica","family":"Piani","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Pediatric Nephrology, Children\u2019s Hospital Colorado, Aurora, CO 80045, USA."},{"name":"Department of Medicine, IRCCS Asiendo Ospedaliero-Universitaria di Bologna, Bologna 40138, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1183-8330","authenticated-orcid":true,"given":"Jonathan","family":"Troost","sequence":"additional","affiliation":[{"name":"Michigan Institute for Clinical and Health Research, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9654-6822","authenticated-orcid":true,"given":"Stefano","family":"Da Sacco","sequence":"additional","affiliation":[{"name":"GOFARR Laboratory for Organ Regenerative Research and Cell Therapeutics in Urology, Saban Research Institute, Division of Urology, Children\u2019s Hospital Los Angeles (CHLA), Los Angeles, CA 90027, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6600-6411","authenticated-orcid":true,"given":"Guadalupe","family":"Rojas-Sanchez","sequence":"additional","affiliation":[{"name":"BloodWorks Northwest, Seattle, WA 98104, USA."},{"name":"Department of Pediatrics, University of Washington, Seattle, WA 98105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3677-4476","authenticated-orcid":true,"given":"Pavel","family":"Davizon-Castillo","sequence":"additional","affiliation":[{"name":"BloodWorks Northwest, Seattle, WA 98104, USA."},{"name":"Department of Pediatrics, University of Washington, Seattle, WA 98105, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6955-6416","authenticated-orcid":true,"given":"Laura","family":"Perin","sequence":"additional","affiliation":[{"name":"GOFARR Laboratory for Organ Regenerative Research and Cell Therapeutics in Urology, Saban Research Institute, Division of Urology, Children\u2019s Hospital Los Angeles (CHLA), Los Angeles, CA 90027, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9915-5376","authenticated-orcid":true,"given":"Ilse","family":"Daehn","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0020-6733","authenticated-orcid":true,"given":"Md Imtiazul","family":"Islam","sequence":"additional","affiliation":[{"name":"Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2256-5793","authenticated-orcid":true,"given":"Audrey","family":"Fetsko","sequence":"additional","affiliation":[{"name":"Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5612-9574","authenticated-orcid":true,"given":"Claudia","family":"Carrera-Mu\u00f1oz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Pediatric Nephrology, Children\u2019s Hospital Colorado, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5639-0210","authenticated-orcid":true,"given":"Brad","family":"Rovin","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Ohio State University, Columbus, OH 43210, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolan L.","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Ohio State University, Columbus, OH 43210, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2481-293X","authenticated-orcid":true,"given":"Mindy","family":"Banks","sequence":"additional","affiliation":[{"name":"Rocky Mountain Pediatric Kidney Center, Rocky Mountain Hospital for Children, Denver, CO 80205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4882-0425","authenticated-orcid":true,"given":"Carmen","family":"de Lucas-Collantes","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Hospital Ni\u00f1o Jesus, Madrid 28009, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5003-9195","authenticated-orcid":true,"given":"Flor A.","family":"Ord\u00f3\u00f1ez-\u00c1lvarez","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Hospital Universitario Central de Asturias, Oviedo 33011, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5188-2455","authenticated-orcid":true,"given":"Cristina","family":"Aparicio-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Hospital Ni\u00f1o Jesus, Madrid 28009, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1163-1831","authenticated-orcid":true,"given":"Miguel A.","family":"Lanaspa","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Andres-Hernando","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4349-2856","authenticated-orcid":true,"given":"Alfons","family":"Segarra","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hospital Universitario Arnau de Vilanova, Lleida 25198, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9368-1356","authenticated-orcid":true,"given":"Cristina","family":"Martinez","sequence":"additional","affiliation":[{"name":"Renal Physiopathology Group, Vall d\u2019Hebron Research Institute (VHIR), Barcelona 08035, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petter","family":"Bjornstad","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Metabolism, and Nutrition, University of Washington School of Medicine, Seattle, WA 98109, USA."},{"name":"Department of Pediatrics, Section of Pediatric Endocrinology, Children\u2019s Hospital Colorado and University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA."},{"name":"Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Scott","family":"Lucia","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7564-9937","authenticated-orcid":true,"given":"Franz","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Division, Heidelberg University Hospital, Heidelberg 69120, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1743-1491","authenticated-orcid":true,"given":"Alev","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Istanbul Faculty of Medicine, Istanbul University, Istanbul 34093, T\u00fcrkiye."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3354-5344","authenticated-orcid":true,"given":"Aleksandra","family":"Zurowska","sequence":"additional","affiliation":[{"name":"Department of Pediatric and Adolescent Nephrology, Medical University of Gdansk, Gdansk 80-210, Poland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1456-335X","authenticated-orcid":true,"given":"Xin","family":"Wang","sequence":"additional","affiliation":[{"name":"Kidney and Urinary Tract Center, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8012-1931","authenticated-orcid":true,"given":"Phillip J.","family":"McCown","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8578-3443","authenticated-orcid":true,"given":"Sean","family":"Eddy","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Hartman","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6055-764X","authenticated-orcid":true,"given":"Laura","family":"Mariani","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4064-0582","authenticated-orcid":true,"given":"Matthias","family":"Kretzler","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1434-6590","authenticated-orcid":true,"given":"Yuwen","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4121-6698","authenticated-orcid":true,"given":"Antonia H. M.","family":"Bouts","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Emma Children\u2019s Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam 1105, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8352-7312","authenticated-orcid":true,"given":"Elena N.","family":"Levtchenko","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Emma Children\u2019s Hospital, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam 1105, Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5778-1512","authenticated-orcid":true,"given":"Julie A.","family":"Dougherty","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William E.","family":"Smoyer","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1756-8271","authenticated-orcid":true,"given":"Bryce A.","family":"Kerlin","sequence":"additional","affiliation":[{"name":"Center for Clinical and Translational Research, Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmoud","family":"Kallash","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Nationwide Children\u2019s Hospital, Columbus, OH 43205, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7019-809X","authenticated-orcid":true,"given":"Danielle E.","family":"Soranno","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Nephrology, Indiana University School of Medicine, Indianapolis, IN 46202, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6269-9692","authenticated-orcid":true,"given":"Jos\u00e9 E.","family":"Cabrera-Sevilla","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Nephrology, Hospital Universitario Santa Lucia, Cartagena 30202, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8863-2007","authenticated-orcid":true,"given":"Juan David","family":"Gonzalez-Rodriguez","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Nephrology, Hospital Universitario Santa Lucia, Cartagena 30202, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bradford J.","family":"Siegele","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital Colorado, Aurora, CO 80045, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3607-8355","authenticated-orcid":true,"given":"Shoji","family":"Tsuji","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kansai Medical University, Osaka 573-1191, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8215-0832","authenticated-orcid":true,"given":"Kazunari","family":"Kaneko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kansai Medical University, Osaka 573-1191, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine B.","family":"Sethna","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Cohen Children\u2019s Medical Center, New York, NY 11042, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8654-0627","authenticated-orcid":true,"given":"Tarak","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Children\u2019s Mercy Hospital, Kansas City, MO 64108, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Bitzer","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1888-728X","authenticated-orcid":true,"given":"Christopher L.","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Michigan, Ann Arbor, MI 48109, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4422-9125","authenticated-orcid":true,"given":"Anna","family":"Dimberg","sequence":"additional","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Rudbeck Laboratory, Uppsala University, Uppsala 75185, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6985-821X","authenticated-orcid":true,"given":"Serena","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liping","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Nephrology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, 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