title: Spectrum of steroid-resistant and congenital nephrotic syndrome in children: the PodoNet registry cohort.
abstract: OBJECTIVE
  Steroid-resistant nephrotic syndrome is a rare kidney disease involving either immune-mediated or genetic alterations of podocyte structure and function. The rare nature, heterogeneity, and slow evolution of the disorder are major obstacles to systematic genotype-phenotype, intervention, and outcome studies, hampering the development of evidence-based diagnostic and therapeutic concepts. To overcome these limitations, the PodoNet Consortium has created an international registry for congenital nephrotic syndrome and childhood-onset steroid-resistant nephrotic syndrome.
  
  
  METHODS
  Since August of 2009, clinical, biochemical, genetic, and histopathologic information was collected both retrospectively and prospectively from 1655 patients with childhood-onset steroid-resistant nephrotic syndrome, congenital nephrotic syndrome, or persistent subnephrotic proteinuria of likely genetic origin at 67 centers in 21 countries through an online portal.
  
  
  RESULTS
  Steroid-resistant nephrotic syndrome manifested in the first 5 years of life in 64% of the patients. Congenital nephrotic syndrome accounted for 6% of all patients. Extrarenal abnormalities were reported in 17% of patients. The most common histopathologic diagnoses were FSGS (56%), minimal change nephropathy (21%), and mesangioproliferative GN (12%). Mutation screening was performed in 1174 patients, and a genetic disease cause was identified in 23.6% of the screened patients. Among 14 genes with reported mutations, abnormalities in NPHS2 (n=138), WT1 (n=48), and NPHS1 (n=41) were most commonly identified. The proportion of patients with a genetic disease cause decreased with increasing manifestation age: from 66% in congenital nephrotic syndrome to 15%-16% in schoolchildren and adolescents. Among various intensified immunosuppressive therapy protocols, calcineurin inhibitors and rituximab yielded consistently high response rates, with 40%-45% of patients achieving complete remission. Confirmation of a genetic diagnosis but not the histopathologic disease type was strongly predictive of intensified immunosuppressive therapy responsiveness. Post-transplant disease recurrence was noted in 25.8% of patients without compared with 4.5% (n=4) of patients with a genetic diagnosis.
  
  
  CONCLUSIONS
  The PodoNet cohort may serve as a source of reference for future clinical and genetic research in this rare but significant kidney disease.
authors: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material.
authors: Agnes
authors: A
authors: Trautmann
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authors: Monica
authors: M
authors: Bodria
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authors: Fatih
authors: F
authors: Ozaltin
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authors: Alaleh
authors: A
authors: Gheisari
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authors: Anette
authors: A
authors: Melk
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authors: Marta
authors: M
authors: Azocar
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authors: Ali
authors: A
authors: Anarat
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authors: Salim
authors: S
authors: Caliskan
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authors: Francesco
authors: F
authors: Emma
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authors: Jutta
authors: J
authors: Gellermann
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authors: Jun
authors: J
authors: Oh
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authors: Esra
authors: E
authors: Baskin
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authors: Joanna
authors: J
authors: Ksiazek
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authors: Giuseppe
authors: G
authors: Remuzzi
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authors: Ozlem
authors: O
authors: Erdogan
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authors: Sema
authors: S
authors: Akman
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authors: Jiri
authors: J
authors: Dusek
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authors: Tinatin
authors: T
authors: Davitaia
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authors: Ozan
authors: O
authors: Özkaya
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authors: Fotios
authors: F
authors: Papachristou
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authors: Agnieszka
authors: A
authors: Firszt-Adamczyk
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authors: Tomasz
authors: T
authors: Urasinski
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authors: Sara
authors: S
authors: Testa
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authors: Rafael T
authors: RT
authors: Krmar
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authors: Lidia
authors: L
authors: Hyla-Klekot
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authors: Andrea
authors: A
authors: Pasini
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authors: Z Birsin
authors: ZB
authors: Özcakar
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authors: Peter
authors: P
authors: Sallay
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authors: Nilgun
authors: N
authors: Cakar
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authors: Monica
authors: M
authors: Galanti
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authors: Joelle
authors: J
authors: Terzic
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authors: Bilal
authors: B
authors: Aoun
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authors: Alberto
authors: A
authors: Caldas Afonso
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authors: Hanna
authors: H
authors: Szymanik-Grzelak
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authors: Beata S
authors: BS
authors: Lipska
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authors: Sven
authors: S
authors: Schnaidt
authors: Due to the number of contributing authors, the affiliations are provided in the Supplemental Material. franz.schaefer@med.uni-heidelberg.de.
authors: Franz
authors: F
authors: Schaefer
mesh_terms: D000293:Adolescent; D017677:Age Distribution; D017668:Age of Onset; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D005060:Europe / Q000453:epidemiology; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D015432:Glomerulonephritis, Membranoproliferative / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D005923:Glomerulosclerosis, Focal Segmental / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D016030:Kidney Transplantation; D007843:Latin America / Q000453:epidemiology; D008297:Male; D008877:Middle East / Q000453:epidemiology; D009154:Mutation; D009402:Nephrosis, Lipoid / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000628:therapy; D010641:Phenotype; D011446:Prospective Studies; D012008:Recurrence; D012042:Registries; D012074:Remission Induction; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D005819:Genetic Markers; D007166:Immunosuppressive Agents
keywords: WT1; children; nephrin; podocin; podocytopathies
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