{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,5]],"date-time":"2026-03-05T23:18:15Z","timestamp":1772752695682,"version":"3.50.1"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:00:00Z","timestamp":1607904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,6,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Idiopathic focal segmental glomerulosclerosis (FSGS) has been linked to immunological and inflammatory response dysregulations. The aim of this study was to find endotypes of FSGS patients using a cluster (CL) analysis based on inflammatory and immunological variables, and to analyse whether a certain endotype is associated with response to treatment with corticosteroids.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This prospective observational study included patients with idiopathic FSGS diagnosed by kidney biopsy. Serum levels of soluble interleukin (IL)-1 receptor, tumoural necrosis factor alpha, Interferon gamma (IFN\u03b3), IL-6, IL-17, IL-12, IL-23, IL-13, IL-4, IL-5, IL-6, haemopexin (Hx), haptoglobin (Hgl), soluble urokinase-type plasminogen activator receptor (suPAR) and urinary CD80 (uCD80) were measured with enzyme-linked immunosorbent assay or nephelometry. T-helper lymphocyte populations and T-regulatory lymphocytes were analysed by flow cytometry. A factorial analysis followed by a k-means CL analysis was performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 79 FSGS patients were included. Three CLs were identified. CL1 (27.8%) included IL-12, IL-17, IL-23 and a T helper 17 (Th17) pattern. CL2 (20.2%) included IL-4, IL-5, IL-13, immunoglobulin E and Th2 pattern. CL3 (51.8%) included IL-6, Hx, Hgl, suPAR and uCD80. There were no differences in age, gender, kidney function, albumin or proteinuria among CLs. About 42\/79 patients (53.1%) showed cortico-resistance. The prevalence of cortico-resistance was significantly lower in CL2 (4\/16, 25%) than in CL1 (16\/26, 72.7%) and CL3 (22\/41, 53.7%) (P = 0.018), with no significant differences between CLs 1 and 3 (P = 0.14).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Patients with FSGS and indistinguishable clinical presentation at diagnosis were classified in three distinct CLs according to predominant Th17, Th2 and acute inflammatory responses that display differences in clinical response to treatment with corticosteroids.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ckj\/sfaa265","type":"journal-article","created":{"date-parts":[[2020,12,9]],"date-time":"2020-12-09T00:10:14Z","timestamp":1607472614000},"page":"1826-1834","source":"Crossref","is-referenced-by-count":6,"title":["Multidimensional inflammatory and immunological endotypes of idiopathic focal segmental glomerulosclerosis and their association with treatment outcomes"],"prefix":"10.1093","volume":"14","author":[{"given":"Neus","family":"Roca","sequence":"first","affiliation":[{"name":"Servicio Nefrologia Pedi\u00e1trica, Hospital Universitari de Vic, Universitat de Vic, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alvaro","family":"Madrid","sequence":"additional","affiliation":[{"name":"Servicio de Nefrolog\u00eda Pedi\u00e1trica, Hospital de Sant Joan de D\u00e9u de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"Lopez","sequence":"additional","affiliation":[{"name":"Servicio de Nefrolog\u00eda Pedi\u00e1trica, Hospital Vall d\u2019Hebr\u00f3n, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gloria","family":"Fraga","sequence":"additional","affiliation":[{"name":"Servicio de Nefrolog\u00eda Pedi\u00e1trica, Hospital Vall d\u2019Hebr\u00f3n, Barcelona, Spain"},{"name":"Servicio de Nefrolog\u00eda Pedi\u00e1trica, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elias","family":"Jatem","sequence":"additional","affiliation":[{"name":"Institut de Recerca Biomedica August Pi Sunyer, Lleida, Barcelona, Spain"},{"name":"Servicio de Nefrologia, Hospital Universitario Arnau de Vilanova, Lleida, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Gonzalez","sequence":"additional","affiliation":[{"name":"Institut de Recerca Biomedica August Pi Sunyer, Lleida, Barcelona, Spain"},{"name":"Servicio de Nefrologia, Hospital Universitario Arnau de Vilanova, Lleida, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Martinez","sequence":"additional","affiliation":[{"name":"Institut de Recerca Biomedica August Pi Sunyer, Lleida, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfons","family":"Segarra","sequence":"additional","affiliation":[{"name":"Institut de Recerca Biomedica August Pi Sunyer, Lleida, Barcelona, Spain"},{"name":"Servicio de Nefrologia, Hospital Universitario Arnau de Vilanova, Lleida, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,12,14]]},"reference":[{"key":"2021063008551241200_sfaa265-B1","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/S0140-6736(03)14184-0","article-title":"Nephrotic syndrome in childhood","volume":"362","author":"Eddy","year":"2003","journal-title":"Lancet"},{"key":"2021063008551241200_sfaa265-B2","doi-asserted-by":"crossref","first-page":"502","DOI":"10.2215\/CJN.05960616","article-title":"Focal segmental glomeruloesclerosis","volume":"12","author":"Rosenberg","year":"2017","journal-title":"Clin J Am Soc Nephrol"},{"key":"2021063008551241200_sfaa265-B3","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1016\/S0140-6736(74)91880-7","article-title":"Pathogenesis of lipoid nephrosis: a disorder of T-cell function","volume":"304","author":"Shalhoub","year":"1974","journal-title":"Lancet"},{"key":"2021063008551241200_sfaa265-B4","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1007\/s00467-009-1214-x","article-title":"T regulatory cell function in idiopathic minimal lesion nephrotic syndrome","volume":"24","author":"Araya","year":"2009","journal-title":"Pediatr Nephrol"},{"key":"2021063008551241200_sfaa265-B5","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.2215\/CJN.03800609","article-title":"Circulating permeability factors in idiopathic nephrotic s\u00edndrome and focal segmental glomeruloesclerosis","volume":"5","author":"McCarthy","year":"2010","journal-title":"Clin J Am Soc Nephrol"},{"key":"2021063008551241200_sfaa265-B6","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1007\/s00467-009-1194-x","article-title":"The prevalence of Th17 cells and FOXP3 regulate T cells (Treg) in children with primary nephrotic syndrome","volume":"24","author":"Shao","year":"2009","journal-title":"Pediatr Nephrol"},{"key":"2021063008551241200_sfaa265-B7","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.coisb.2017.04.003","article-title":"Treatable traits and therapeutic targets: goals for systems biology in infectious disease","volume":"2","author":"Russell","year":"2017","journal-title":"Curr Opin Syst Biol"},{"key":"2021063008551241200_sfaa265-B8","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1016\/j.mehy.2006.04.072","article-title":"The nephrotic syndrome is an immunoinflammatory disorder","volume":"68","author":"Camici","year":"2007","journal-title":"Med Hypotheses"},{"key":"2021063008551241200_sfaa265-B9","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1007\/s00467-004-1569-y","article-title":"Up-regulation of interleukin-2 mRNA in children with idiopathic nephrotic syndrome","volume":"19","author":"Shimoyama","year":"2004","journal-title":"Pediatr Nephrol"},{"key":"2021063008551241200_sfaa265-B10","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1111\/j.1365-2362.1994.tb02022.x","article-title":"Increase of tumour necrosis factor \u03b1 synthesis and gene expression in peripheral blood mononuclear cells of children with idiopathic nephrotic syndrome","volume":"24","author":"Bustos","year":"1994","journal-title":"Eur J Clin Invest"},{"key":"2021063008551241200_sfaa265-B11","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1007\/s10157-010-0330-z","article-title":"Th2 cells predominate in idiopathic steroid-sensitive nephrotic syndrome","volume":"14","author":"Kanai","year":"2010","journal-title":"Clin Exp Nephrol"},{"key":"2021063008551241200_sfaa265-B12","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/S0272-6386(12)80742-6","article-title":"Elevated levels of tumor necrosis factor-\u03b1 in the nephrotic syndrome in humans","volume":"21","author":"Suranyi","year":"1993","journal-title":"Am J Kidney Dis"},{"key":"2021063008551241200_sfaa265-B13","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1159\/000072065","article-title":"Interleukin-8 and tumor necrosis factor-alpha are increased in minimal change disease but do not alter albumin permeability","volume":"23","author":"Cho","year":"2003","journal-title":"Am J Nephrol"},{"key":"2021063008551241200_sfaa265-B14","first-page":"993","article-title":"Serum interleukins and urinary microglobulin in children with idiopathic nephrotic syndrome","volume":"11","author":"Rizk","year":"2005","journal-title":"East Mediterr Health J"},{"key":"2021063008551241200_sfaa265-B15","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1159\/000350161","article-title":"The role of Th17\/IL-17 in the pathogenesis of primary nephrotic syndrome in children","volume":"37","author":"Wang","year":"2013","journal-title":"Kidney Blood Press Res"},{"key":"2021063008551241200_sfaa265-B16","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/ki.2014.197","article-title":"Soluble urokinase receptor is a biomarker of cardiovascular disease in chronic kidney disease","volume":"87","author":"Meijers","year":"2015","journal-title":"Kidney Int"},{"key":"2021063008551241200_sfaa265-B17","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s00467-014-2892-6","article-title":"Serum suPAR levels help differentiate steroid resistance from steroid-sensitive nephrotic syndrome in children","volume":"30","author":"Peng","year":"2015","journal-title":"Pediatr Nephrol"},{"key":"2021063008551241200_sfaa265-B18","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1681\/ASN.2006070710","article-title":"Overexpression of interleukin-13 induces minimal-change-like nephropathy in rats","volume":"18","author":"Lai","year":"2007","journal-title":"J Am Soc Nephrol"},{"key":"2021063008551241200_sfaa265-B19","first-page":"141","article-title":"KDIGO clinical practice guideline for glomerulonephritis","volume":"2","author":"Eknoyan","year":"2012","journal-title":"Kidney Int Suppl"},{"key":"2021063008551241200_sfaa265-B20","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1016\/j.trsl.2015.03.002","article-title":"Janus kinase 2\/signal transducer and activator of transcription 3 inhibitors attenuate the effect of cardiotrophin-like cytokine factor 1 and human focal segmental glomerulosclerosis serum on glomerular filtration barrier","volume":"166","author":"Sharma","year":"2015","journal-title":"Transl Res"},{"key":"2021063008551241200_sfaa265-B21","doi-asserted-by":"crossref","first-page":"2145","DOI":"10.1093\/ndt\/17.12.2145","article-title":"Transforming growth factor-beta(1) in the kidney and urine of patients with glomerular disease and proteinuria","volume":"17","author":"Goumenos","year":"2002","journal-title":"Nephrol Dial Transplant"},{"key":"2021063008551241200_sfaa265-B22","doi-asserted-by":"crossref","first-page":"393","DOI":"10.5414\/CNP58393","article-title":"Th1\/Th2 balance in childhood idiopathic nephrotic syndrome","volume":"58","author":"Kaneko","year":"2002","journal-title":"Clin Nephrol"},{"key":"2021063008551241200_sfaa265-B23","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1007\/s00467-017-3677-5","article-title":"Immunology of idiopathic nephrotic s\u00edndrome","volume":"33","author":"Colucci","year":"2018","journal-title":"Pediatr Nephrol"},{"key":"2021063008551241200_sfaa265-B24","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1186\/1824-7288-39-42","article-title":"CD19+CD23+ cells, CD4+CD25+ T cells, E-selectin and interleukin-12 levels in children with steroid sensitive nephrotic syndrome","volume":"39","author":"Yildiz","year":"2013","journal-title":"Ital J Pediatr"},{"key":"2021063008551241200_sfaa265-B25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000075574","article-title":"Regulation of plasma hemopexin activity by stimulated endothelial or mesangial cells","volume":"96","author":"Kapojos","year":"2004","journal-title":"Nephron Physiol"},{"key":"2021063008551241200_sfaa265-B26","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1046\/j.1523-1755.2000.00996.x","article-title":"Induction of experimental proteinuria in vivo following infusion of human plasma hemopexin","volume":"57","author":"Cheung","year":"2000","journal-title":"Kidney Int"},{"key":"2021063008551241200_sfaa265-B27","first-page":"227","article-title":"Value of determination of haptoglobin and alpha1-antitripsina in predicting response to glucocorticoid therapy in children with primary nephrotic syndrome","volume":"17","author":"Yang","year":"2015","journal-title":"Zhong Dang Dai Zhi"},{"key":"2021063008551241200_sfaa265-B28","doi-asserted-by":"crossref","first-page":"1467","DOI":"10.1007\/s00467-014-2840-5","article-title":"CD80 and suPAR in patients with minimal change disease and focal segmental glomerulosclerosis: diagnostic and pathogenic significance: response","volume":"29","author":"Cara-Fuentes","year":"2014","journal-title":"Pediatr Nephrol"},{"key":"2021063008551241200_sfaa265-B29","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1016\/j.ijcard.2012.03.040","article-title":"CRP and suPAR are differently related to anthropometry and subclinical organ damage","volume":"167","author":"Lyngb\u00e6k","year":"2013","journal-title":"Int J Cardiol"},{"key":"2021063008551241200_sfaa265-B30","first-page":"1143","article-title":"Activation of the acute inflammatory phase response in idiopathic nephrotic syndrome: association with clinicopathological phenotypes ad with response to corticosteroids","volume":"39","author":"Roca","year":"2002","journal-title":"Clin Kidney J"},{"key":"2021063008551241200_sfaa265-B31","first-page":"146","article-title":"A. Effect of IL-6 C-174G polymorphism on response to steroid therapy in Egyptian children with nephrotic syndrome","volume":"5","author":"El Hussiny","year":"2018","journal-title":"Eur J Pharm Med Res"},{"key":"2021063008551241200_sfaa265-B32","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/S0091-6749(97)70255-0","article-title":"Corticosteroid modulation of human, antigen-specific Thl and Th2 responses","volume":"100","author":"Braun","year":"1997","journal-title":"J Allergy Clin Immunol"}],"container-title":["Clinical Kidney Journal"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ckj\/advance-article-pdf\/doi\/10.1093\/ckj\/sfaa265\/36185855\/sfaa265.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ckj\/article-pdf\/14\/7\/1826\/38822092\/sfaa265.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ckj\/article-pdf\/14\/7\/1826\/38822092\/sfaa265.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,30]],"date-time":"2021-06-30T04:57:44Z","timestamp":1625029064000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ckj\/article\/14\/7\/1826\/6033662"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,14]]},"references-count":32,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2020,12,14]]},"published-print":{"date-parts":[[2021,6,24]]}},"URL":"https:\/\/doi.org\/10.1093\/ckj\/sfaa265","relation":{},"ISSN":["2048-8513"],"issn-type":[{"value":"2048-8513","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,7,1]]},"published":{"date-parts":[[2020,12,14]]}}}