{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T12:18:37Z","timestamp":1793881117284,"version":"4.7.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"12","funder":[{"DOI":"10.13039\/501100000241","name":"Physicians' Services Incorporated Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000241","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100006126","name":"Hospital for Sick Children","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100006126","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Women's College Research Institute"},{"name":"Cure Glomerulopathy","award":["Career Development Fellowship program"],"award-info":[{"award-number":["Career Development Fellowship program"]}]},{"name":"SickKids Clinician-Scientist Training program"},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"crossref","award":["Research Fellowship program"],"award-info":[{"award-number":["Research Fellowship program"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000191","name":"Kidney Foundation of Canada","doi-asserted-by":"crossref","award":["KRESCENT program"],"award-info":[{"award-number":["KRESCENT program"]}],"id":[{"id":"10.13039\/501100000191","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["CJASN"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Key Points<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Three quarters of children with steroid-resistant nephrotic syndrome respond to other immunosuppression and have good kidney outcomes.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Children classified as frequently relapsing by International Pediatric Nephrology Association versus Kidney Disease Improving Global Outcomes criteria have similar relapse rates and risk of CKD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>These findings support defining treatment resistance by response to any immunosuppression and implementing the International Pediatric Nephrology Association criteria for frequent relapses.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>In childhood nephrotic syndrome, definitions of immunosuppression response, frequently relapsing nephrotic syndrome (FRNS), and long-term remission are conflicting and based on limited evidence. Our goal was to define treatment response, FRNS, and long-term remission on the basis of associated disease outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We included children (6 months\u201318 years) diagnosed with nephrotic syndrome between 1993 and 2023 in combined Canadian cohorts. We evaluated different definitions of (\n                      <jats:italic toggle=\"yes\">1<\/jats:italic>\n                      ) immunosuppressive treatment response, (\n                      <jats:italic toggle=\"yes\">2<\/jats:italic>\n                      ) FRNS, including Kidney Disease Improving Global Outcomes (KDIGO) 2021 and International Pediatric Nephrology Association (IPNA) 2023 criteria, and (\n                      <jats:italic toggle=\"yes\">3<\/jats:italic>\n                      ) long-term remission. Outcomes were time to CKD, relapse count throughout follow-up, and time to relapse, analyzed by Cox proportional hazards and negative binomial regression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We included 1114 children with nephrotic syndrome (median age at diagnosis, 3.8 years; 63% male; median follow-up, 4.7 years). Among them, 1054 (95%) were steroid sensitive, 60 (5%) were steroid resistant (steroid-resistant nephrotic syndrome [SRNS]), and 73% with SRNS achieved complete remission with steroid-sparing immunosuppression. No child with treatment-responsive SRNS developed CKD. Within 1 year of diagnosis, 281 steroid-sensitive children (27%) were classified with FRNS by KDIGO and 383 (36%) by IPNA criteria. Children with FRNS by IPNA criteria (versus KDIGO) had a similar number of relapses (adjusted rate ratio, 0.95; 95% confidence interval, 0.81 to 1.12) and CKD risk (2% each) but less often received steroid-sparing immunosuppression (hazard ratio, 0.42; 95% confidence interval, 0.32 to 0.56). Ninety-eight percent of relapses occur within 3 years of the initial diagnosis or the last relapse event.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Children with SRNS who achieve remission have a similar CKD risk to steroid-sensitive children. Children with FRNS by IPNA 2023 and KDIGO 2021 criteria experience similar rates of relapse and CKD. This supports defining treatment resistance by response to any immunosuppressive medication, implementation of the IPNA FRNS criteria, and use of 3-year relapse-free survival as a surrogate for long-term remission.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2215\/cjn.0000000842","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T16:00:23Z","timestamp":1760544023000},"page":"1767-1779","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":9,"title":["Challenging Clinical Practice Guideline Definitions in Childhood Nephrotic Syndrome"],"prefix":"10.2215","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2223-0646","authenticated-orcid":false,"given":"Cal H.","family":"Robinson","sequence":"first","affiliation":[{"name":"Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada"},{"name":"Child Health Evaluative Sciences, Research Institute, The 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Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6345-1584","authenticated-orcid":false,"given":"Vaneet","family":"Dhillon","sequence":"additional","affiliation":[{"name":"Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5472-7920","authenticated-orcid":false,"given":"Mackenzie","family":"Garner","sequence":"additional","affiliation":[{"name":"Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4168-3277","authenticated-orcid":false,"given":"Christoph","family":"Licht","sequence":"additional","affiliation":[{"name":"Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, 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Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5994-0799","authenticated-orcid":false,"given":"Chia Wei","family":"Teoh","sequence":"additional","affiliation":[{"name":"Division of Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada"},{"name":"Department of Pediatrics, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1465-2523","authenticated-orcid":false,"given":"Jovanka","family":"Vasilevska-Ristovska","sequence":"additional","affiliation":[{"name":"Child Health Evaluative Sciences, Research Institute, The Hospital for Sick Children, Toronto, Ontario, Canada"},{"name":"Department of Medicine, Women's College Hospital, Toronto, Ontario, 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