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The existence of circulating factor disease (CFD) as a driver of NS has been epitomised by a subset of patients who exhibit disease recurrence after transplantation, alongside laboratory work. Several circulating factors have been proposed and studied, broadly grouped into protease components such as soluble urokinase-type plasminogen activator (suPAR), hemopexin (Hx) and calcium\/calmodulin-serine protease kinase (CASK), and other circulating proteases, and immune components such as TNF-\u03b1, CD40 and cardiotrophin-like cytokine-1 (CLC-1). While currently there is no definitive way of assessing risk of CFD pre-transplantation, promising work is emerging through the study of \u2018multi-omic\u2019 bioinformatic data from large national cohorts and biobanks.<\/jats:p>","DOI":"10.1007\/s00467-023-05928-8","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T07:04:09Z","timestamp":1679555049000},"page":"3513-3518","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["What is circulating factor disease and how is it currently explained?"],"prefix":"10.1007","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3234-7549","authenticated-orcid":false,"given":"Samantha","family":"Hayward","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5222-6341","authenticated-orcid":false,"given":"Kevon","family":"Parmesar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9808-4518","authenticated-orcid":false,"given":"Moin A.","family":"Saleem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"key":"5928_CR1","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1016\/S0140-6736(74)91880-7","volume":"2","author":"RJ Shalhoub","year":"1974","unstructured":"Shalhoub RJ (1974) Pathogenesis of lipoid nephrosis: a disorder of T-cell function. 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