title: Immunosuppression and renal outcome in congenital and pediatric steroid-resistant nephrotic syndrome.
abstract: OBJECTIVE
  Mutations in podocyte genes are associated with steroid-resistant nephrotic syndrome (SRNS), mostly affecting younger age groups. To date, it is unclear whether these patients benefit from intensified immunosuppression with cyclosporine A (CsA). The aim of this study was to evaluate the influence of podocyte gene defects in congenital nephrotic syndrome (CNS) and pediatric SRNS on the efficacy of CsA therapy and preservation of renal function.
  
  
  METHODS
  Genotyping was performed in 91 CNS/SRNS patients, irrespective of age at manifestation or response to CsA.
  
  
  RESULTS
  Mutations were identified in 52% of families (11 NPHS1, 17 NPHS2, 11 WT1, 1 LAMB2, 3 TRPC6). Sixty-eight percent of patients with nongenetic SRNS responded to CsA, most of them achieved complete remission. In contrast, none of the patients with genetic CNS/SRNS experienced a complete remission and only two (17%) achieved a partial response, both affected by a WT1 mutation. Preservation of renal function was significantly better in children with nongenetic disease after a mean follow-up time of 8.6 years (ESRD in 29% versus 71%).
  
  
  CONCLUSIONS
  The mutation detection rate in our population was high (52%). Most patients with genetic CNS/SRNS did not benefit from CsA with significantly lower response rates compared with nongenetic patients and showed rapid progression to end-stage renal failure. These data strongly support the idea not to expose CNS/SRNS patients with inherited defects related to podocyte function to intensified immunosuppression with CsA.
authors.affiliation: Pediatric Nephrology, Pediatrics II, University of Duisburg-Essen, Essen, Germany.
authors.forename: Anja K
authors.initials: AK
authors.lastname: Büscher
authors.forename: Birgitta
authors.initials: B
authors.lastname: Kranz
authors.forename: Rainer
authors.initials: R
authors.lastname: Büscher
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
authors.forename: Bernd
authors.initials: B
authors.lastname: Dworniczak
authors.forename: Petra
authors.initials: P
authors.lastname: Pennekamp
authors.forename: Eberhard
authors.initials: E
authors.lastname: Kuwertz-Bröking
authors.forename: Anne-Margret
authors.initials: AM
authors.lastname: Wingen
authors.forename: Ulrike
authors.initials: U
authors.lastname: John
authors.forename: Markus
authors.initials: M
authors.lastname: Kemper
authors.forename: Leo
authors.initials: L
authors.lastname: Monnens
authors.forename: Peter F
authors.initials: PF
authors.lastname: Hoyer
authors.forename: Stefanie
authors.initials: S
authors.lastname: Weber
authors.forename: Martin
authors.initials: M
authors.lastname: Konrad
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004351:Drug Resistance; D005260:Female; D016162:Genes, Wilms Tumor; D020022:Genetic Predisposition to Disease; D005858:Germany; D040941:Heredity; D006776:Hospitals, Pediatric; D006785:Hospitals, University; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D007797:Laminin / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D009404:Nephrotic Syndrome / Q000151:congenital / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D018579:Patient Selection; D010641:Phenotype; D012189:Retrospective Studies; D013256:Steroids / Q000627:therapeutic use*; D050052:TRPC Cation Channels / Q000235:genetics; D000074287:TRPC6 Cation Channel; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; D007797:Laminin; D008565:Membrane Proteins; C407223:NPHS2 protein; D013256:Steroids; D050052:TRPC Cation Channels; D000074287:TRPC6 Cation Channel; C117032:TRPC6 protein, human; C113267:nephrin; C058783:laminin beta2; D016572:Cyclosporine
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