{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T11:20:16Z","timestamp":1790508016304,"version":"4.1.0"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","funder":[{"DOI":"10.13039\/501100000883","name":"University of Bristol","doi-asserted-by":"publisher","award":["204813\/Z\/16\/Z (to A.E.M)"],"award-info":[{"award-number":["204813\/Z\/16\/Z (to A.E.M)"]}],"id":[{"id":"10.13039\/501100000883","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MRC\/R013942\/1 (to M.A.S)"],"award-info":[{"award-number":["MRC\/R013942\/1 (to M.A.S)"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000291","name":"Kidney Research UK","doi-asserted-by":"publisher","award":["PDF_005_20171124 (to A.B)"],"award-info":[{"award-number":["PDF_005_20171124 (to A.B)"]}],"id":[{"id":"10.13039\/501100000291","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/P024297\/1 (to M.A.S)"],"award-info":[{"award-number":["MR\/P024297\/1 (to M.A.S)"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health Research","doi-asserted-by":"publisher","award":["To E.S.S"],"award-info":[{"award-number":["To E.S.S"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Nephrotic Syndrome Trust","award":["To M.A.S"],"award-info":[{"award-number":["To M.A.S"]}]},{"DOI":"10.13039\/100004440","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["204813\/Z\/16\/Z (to A.E.M)"],"award-info":[{"award-number":["204813\/Z\/16\/Z (to A.E.M)"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background and objectives<\/jats:title>\n                    <jats:p>Intensified immunosuppression in steroid-resistant nephrotic syndrome is broadly applied, with disparate outcomes. This review of patients from the United Kingdom National Study of Nephrotic Syndrome cohort aimed to improve disease stratification by determining, in comprehensively genetically screened patients with steroid-resistant nephrotic syndrome, if there is an association between response to initial intensified immunosuppression and disease progression and\/or post-transplant recurrence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design, setting, participants, &amp; measurements<\/jats:title>\n                    <jats:p>\n                      Pediatric patients with steroid-resistant nephrotic syndrome were recruited\n                      <jats:italic toggle=\"yes\">via<\/jats:italic>\n                      the UK National Registry of Rare Kidney Diseases. All patients were whole-genome sequenced, whole-exome sequenced, or steroid-resistant nephrotic syndrome gene-panel sequenced. Complete response or partial response within 6 months of starting intensified immunosuppression was ascertained using laboratory data. Response to intensified immunosuppression and outcomes were analyzed according to genetic testing results, pattern of steroid resistance, and first biopsy findings.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 271 patients, 178 (92 males, median onset age 4.7 years) received intensified immunosuppression with response available. A total of 4% of patients with monogenic disease showed complete response, compared with 25% of genetic-testing-negative patients (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.02). None of the former recurred post-transplantation. In genetic-testing-negative patients, 97% with complete response to first intensified immunosuppression did not progress, whereas 44% of nonresponders developed kidney failure with 73% recurrence post-transplant. Secondary steroid resistance had a higher complete response rate than primary\/presumed resistance (43% versus 23%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.001). The highest complete response rate in secondary steroid resistance was to rituximab (64%). Biopsy results showed no correlation with intensified immunosuppression response or outcome.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Patients with monogenic steroid-resistant nephrotic syndrome had a poor therapeutic response and no post-transplant recurrence. In genetic-testing-negative patients, there was an association between response to first intensified immunosuppression and long-term outcome. Patients with complete response rarely progressed to kidney failure, whereas nonresponders had poor kidney survival and a high post-transplant recurrence rate. Patients with secondary steroid resistance were more likely to respond, particularly to rituximab.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.13371019","type":"journal-article","created":{"date-parts":[[2020,4,21]],"date-time":"2020-04-21T13:13:14Z","timestamp":1587474794000},"page":"983-994","source":"Crossref","is-referenced-by-count":51,"title":["Response to First Course of Intensified Immunosuppression in Genetically Stratified Steroid Resistant Nephrotic Syndrome"],"prefix":"10.2215","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7920-8186","authenticated-orcid":false,"given":"Anna E.","family":"Mason","sequence":"first","affiliation":[{"name":"Bristol Renal, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0135-6546","authenticated-orcid":false,"given":"Ethan S.","family":"Sen","sequence":"additional","affiliation":[{"name":"Bristol Renal, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Bierzynska","sequence":"additional","affiliation":[{"name":"Bristol Renal, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Colby","sequence":"additional","affiliation":[{"name":"Bristol Renal, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Afzal","sequence":"additional","affiliation":[{"name":"Bristol Renal, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Dorval","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Reference Center for Hereditary Kidney Diseases, Necker Hospital, Assistance Publique\u2014H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ania B.","family":"Koziell","sequence":"additional","affiliation":[{"name":"Division of Transplantation Immunology and Mucosal Biology, Department of Experimental Immunobiology, Faculty of Life Sciences and Medicine, King\u2019s College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie","family":"Williams","sequence":"additional","affiliation":[{"name":"Bristol Genetics Laboratory, Pathology Sciences, Southmead Hospital, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Boyer","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Reference Center for Hereditary Kidney Diseases, Necker Hospital, Assistance Publique\u2014H\u00f4pitaux de Paris, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gavin I.","family":"Welsh","sequence":"additional","affiliation":[{"name":"Bristol Renal, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moin A.","family":"Saleem","sequence":"additional","affiliation":[{"name":"Bristol Renal, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the UK RaDaR\/NephroS 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[published correction appears in Clin Exp Pharmacol Physiol 46: 788, 2019]","author":"Zachwieja","year":"2018","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"B49-20230813","doi-asserted-by":"crossref","first-page":"1117","DOI":"10.1681\/ASN.2011080775","article-title":"Rituximab in children with resistant idiopathic nephrotic syndrome","volume":"23","author":"Magnasco","year":"2012","journal-title":"J Am Soc Nephrol"},{"key":"B50-20230813","doi-asserted-by":"crossref","first-page":"85ra46","DOI":"10.1126\/scitranslmed.3002231","article-title":"Rituximab targets podocytes in recurrent focal segmental glomerulosclerosis","volume":"3","author":"Fornoni","year":"2011","journal-title":"Sci Transl Med"}],"container-title":["Clinical Journal of the American Society of Nephrology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ovid.com\/10.2215\/CJN.13371019","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T13:39:45Z","timestamp":1786369185000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ovid.com\/10.2215\/CJN.13371019"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4,21]]},"references-count":48,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2020]]}},"URL":"https:\/\/doi.org\/10.2215\/cjn.13371019","relation":{},"ISSN":["1555-9041","1555-905X"],"issn-type":[{"value":"1555-9041","type":"print"},{"value":"1555-905X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4,21]]}}}