{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,2,21]],"date-time":"2025-02-21T03:14:49Z","timestamp":1740107689146,"version":"3.37.3"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"9","license":[{"start":{"date-parts":[[2020,5,23]],"date-time":"2020-05-23T00:00:00Z","timestamp":1590192000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,5,23]],"date-time":"2020-05-23T00:00:00Z","timestamp":1590192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100006209","name":"Radboud University Medical Center","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006209","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pediatr Nephrol"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>The C3 glomerulopathies (C3G) are recently defined glomerular diseases, attributed to abnormal complement regulation. Dense deposit disease (DDD) is part of the spectrum of C3G, characterized by electron-dense deposits in the lamina densa of the glomerular basement membrane. Patients with DDD present with hematuria, variable degrees of proteinuria, and kidney dysfunction. Kidney biopsies typically disclose proliferative and inflammatory patterns of injury. Treatment with glucocorticoids and mycophenolate mofetil has been shown to achieve remission of proteinuria in a significant proportion of C3G patients.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Case-diagnosis\/treatment<\/jats:title>\n<jats:p>We report two patients with persistent nephrotic syndrome while on immunosuppressive therapy. Repeat kidney biopsies disclosed massive C3 deposits with foot process effacement in the absence of proliferative or inflammatory lesions on light microscopy.<\/jats:p>\n<\/jats:sec><jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>These cases, coupled with data from animal models of disease and the variable response to eculizumab in C3G patients, illustrate that two different pathways might be involved in the development of kidney injury in C3G: a C5-independent pathway leading to glomerular capillary wall injury and the development of proteinuria versus a C5-dependent pathway that causes proliferative glomerulonephritis and kidney dysfunction.<\/jats:p>\n<\/jats:sec>","DOI":"10.1007\/s00467-020-04600-9","type":"journal-article","created":{"date-parts":[[2020,5,23]],"date-time":"2020-05-23T09:02:31Z","timestamp":1590224551000},"page":"1791-1795","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Treatment-resistant nephrotic syndrome in dense deposit disease: complement-mediated glomerular capillary wall injury?"],"prefix":"10.1007","volume":"35","author":[{"given":"Caroline","family":"Duineveld","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric J.","family":"Steenbergen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew S.","family":"Bomback","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole C. A. J.","family":"van de Kar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jack F. M.","family":"Wetzels","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,5,23]]},"reference":[{"key":"4600_CR1","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1007\/s00467-015-3310-4","volume":"32","author":"M Riedl","year":"2017","unstructured":"Riedl M, Thorner P, Licht C (2017) C3 Glomerulopathy. 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N.C.A.J.K. and J.F.M.W. are members of the Alexion Scientific Advisory Board of aHUS and received consultation and speaker\u2019s fees. A.S.B. has received consulting fees from Achillion, ChemoCentryx, and Novartis. All pharmaceutical companies had no role in study design; collection, analysis, and interpretation of data; writing the report; and the decision to submit the report for publication. C.D., N.C.A.J.K., and J.F.M.W. participate in clinical trials for complement-mediated disease funded by ChemoCentryx and Achillion. The authors declare that they have no other relevant financial interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This case series involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. According to the Dutch law, no approval from the ethical medical committee was necessary.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from both participants included in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The participants signed informed consent regarding publishing their data and images of the kidney biopsies.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}}]}}