{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T20:31:19Z","timestamp":1786480279202,"version":"build-2736575974"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","funder":[{"DOI":"10.13039\/501100001700","name":"Ministry of Education, Culture, Sports, Science and Technology of Japan","doi-asserted-by":"crossref","award":["20K16926"],"award-info":[{"award-number":["20K16926"]}],"id":[{"id":"10.13039\/501100001700","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Kidney360"],"published-print":{"date-parts":[[2022,8,25]]},"abstract":"\n Key Points<\/jats:title>\n \n \n \n We investigated the association between focal segmental glomerulosclerosis histologic variants (Columbia classification) and monogenic variant detection rates.<\/jats:p>\n <\/jats:list-item>\n \n The perihilar variants had the strongest association with detection of monogenic variants.<\/jats:p>\n <\/jats:list-item>\n \n The tip variants had the weakest association with detection of monogenic variants.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n Approximately 30% of children with steroid-resistant nephrotic syndrome (SRNS) have causative monogenic variants. SRNS represents glomerular disease resulting from various etiologies, which lead to similar patterns of glomerular damage. Patients with SRNS mainly exhibit focal segmental glomerulosclerosis (FSGS). There is limited information regarding associations between histologic variants of FSGS (diagnosed using on the Columbia classification) and monogenic variant detection rates or clinical characteristics. Here, we report FSGS characteristics in a large population of affected patients.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n This retrospective study included 119 patients with FSGS, diagnosed using the Columbia classification; all had been referred to our hospital for genetic testing from 2016 to 2021. We conducted comprehensive gene screening of all patients using a targeted next-generation sequencing panel that included 62 podocyte-related genes. Data regarding patients\u2019 clinical characteristics and pathologic findings were obtained from referring clinicians. We analyzed the associations of histologic variants with clinical characteristics, kidney survival, and gene variant detection rates.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The distribution of histologic variants according to the Columbia classification was 45% (\n n<\/jats:italic>\n =53) FSGS not otherwise specified, 21% (\n n<\/jats:italic>\n =25) cellular, 15% (\n n<\/jats:italic>\n =18) perihilar, 13% (\n n<\/jats:italic>\n =16) collapsing, and 6% (\n n<\/jats:italic>\n =7) tip. The median age at end stage kidney disease onset was 37 years; there were no differences in onset age among variants. We detected monogenic disease-causing variants involving 12 of the screened podocyte-related genes in 34% (40 of 119) of patients. The most common genes were\n WT1<\/jats:italic>\n (23%),\n INF2<\/jats:italic>\n (20%),\n TRPC6<\/jats:italic>\n (20%), and\n ACTN4<\/jats:italic>\n (10%). The perihilar and tip variants had the strongest and weakest associations with detection of monogenic variants (83% and 0%, respectively;\n P<\/jats:italic>\n <0.001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n We revealed the distributions of histologic variants of genetic FSGS and nongenetic FSGS in a large patient population. Detailed data concerning gene variants and pathologic findings are important for understanding the etiology of FSGS.<\/jats:p>\n <\/jats:sec>","DOI":"10.34067\/kid.0000812022","type":"journal-article","created":{"date-parts":[[2022,5,24]],"date-time":"2022-05-24T17:55:15Z","timestamp":1653414915000},"page":"1384-1393","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":17,"title":["Clinical, Pathological, and Genetic Characteristics in Patients with Focal Segmental Glomerulosclerosis"],"prefix":"10.34067","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4946-1345","authenticated-orcid":false,"given":"China","family":"Nagano","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeo","family":"Hara","sequence":"additional","affiliation":[{"name":"Department of Diagnostic Pathology, Kobe City Medical Center General Hospital, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norishige","family":"Yoshikawa","sequence":"additional","affiliation":[{"name":"Clinical Research Center, Takatsuki General Hospital, Takatsuki, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Asami","family":"Takeda","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7993-361X","authenticated-orcid":false,"given":"Yoshimitsu","family":"Gotoh","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Japanese Red Cross Aichi Medical Center Nagoya Daini Hospital, Nagoya, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7151-459X","authenticated-orcid":false,"given":"Riku","family":"Hamada","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Tokyo Metropolitan Children\u2019s Medical Center, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Department of Pathology, Tokyo Metropolitan Children\u2019s Medical Center, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Seirei-Hamamatsu General Hospital, Hamamatsu, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuichiro","family":"Fujinaga","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Saitama Children\u2019s Medical Center, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koji","family":"Sakuraya","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Saitama Children\u2019s Medical Center, Saitama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3528-6961","authenticated-orcid":false,"given":"Koichi","family":"Kamei","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2015-9073","authenticated-orcid":false,"given":"Yuko","family":"Hamasaki","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Faculty of Medicine, Toho University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideyo","family":"Oguchi","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Faculty of Medicine, Toho University, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0700-9177","authenticated-orcid":false,"given":"Yoshinori","family":"Araki","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, National Hospital Organization Hokkaido Medical Center, Hokkaido, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayoi","family":"Ogawa","sequence":"additional","affiliation":[{"name":"Hokkaido Renal Pathology Center, Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6029-451X","authenticated-orcid":false,"given":"Takayuki","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5242-8987","authenticated-orcid":false,"given":"Shuichi","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seiji","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Child Health, Kurume University School of Medicine, Kurume, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5458-0088","authenticated-orcid":false,"given":"Hiroshi","family":"Kaito","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hyogo Prefectural Kobe Children\u2019s Hospital, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuya","family":"Aoto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Ishiko","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rini","family":"Rossanti","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8387-8008","authenticated-orcid":false,"given":"Nana","family":"Sakakibara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1655-6030","authenticated-orcid":false,"given":"Tomoko","family":"Horinouchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6107-1169","authenticated-orcid":false,"given":"Tomohiko","family":"Yamamura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9454-9680","authenticated-orcid":false,"given":"Hiroaki","family":"Nagase","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, 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History"}},{"value":"2022-04-27","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}