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However, it is not yet known whether these factors are involved in mediating sodium retention in nephrotic syndrome (NS). Here we used a genetic mouse model of NS based on an inducible podocin deletion (\n                    <jats:italic>Nphs2<\/jats:italic>\n                    <jats:sup>\u0394ipod<\/jats:sup>\n                    ). These mice were intercrossed with mice deficient for FB, FD or C3, yielding\n                    <jats:italic>Nphs2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u0394ipod<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>*Cfb<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    ,\n                    <jats:italic>Nphs2<\/jats:italic>\n                    <jats:sup>\u0394ipod<\/jats:sup>\n                    <jats:italic>*Cfd<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    <jats:italic>or Nphs2<\/jats:italic>\n                    <jats:sup>\u0394ipod<\/jats:sup>\n                    <jats:italic>*C3<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u2212\/\u2212<\/jats:italic>\n                    <\/jats:sup>\n                    mice, respectively. NS was induced after oral doxycycline treatment for 14 days. C3, FB and FD were detected in the nephrotic urine of\n                    <jats:italic>Nphs2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>\u0394ipod<\/jats:italic>\n                    <\/jats:sup>\n                    mice as well as fragments of C3 and FB, indicating intrarenal activation of the alternative complement pathway. Lack of FB and FD had no impact on the activation of C3. Immunohistochemistry demonstrated positive C3 staining in protein casts and within the proximal tubule. Nephrotic mice of all genotypes experienced similar proteolytic activation of the epithelial sodium channel ENaC, developed sodium retention (urinary sodium concentration\u2009&lt;\u200920 mM) and body weight gain. This was associated with a stimulation of proteolytic processing of epithelial sodium channel ENaC in all genotypes. In conclusion, components of the alternative complement pathway are detectable and activated in nephrotic syndrome. Mice with deletion of C3, FB or FD are not protected from proteolytic ENaC activation and sodium retention in NS.\n                  <\/jats:p>","DOI":"10.1007\/s00424-025-03136-x","type":"journal-article","created":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T09:48:04Z","timestamp":1767433684000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Activation of the alternative complement pathway and its relevance for sodium retention in experimental nephrotic syndrome"],"prefix":"10.1007","volume":"478","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1473-377X","authenticated-orcid":false,"given":"Daniel","family":"Essigke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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