title: Rapid Response to Cyclosporin A and Favorable Renal Outcome in Nongenetic Versus Genetic Steroid-Resistant Nephrotic Syndrome.
abstract: OBJECTIVE
  Treatment of congenital nephrotic syndrome (CNS) and steroid-resistant nephrotic syndrome (SRNS) is demanding, and renal prognosis is poor. Numerous causative gene mutations have been identified in SRNS that affect the renal podocyte. In the era of high-throughput sequencing techniques, patients with nongenetic SRNS frequently escape the scientific interest. We here present the long-term data of the German CNS/SRNS Follow-Up Study, focusing on the response to cyclosporin A (CsA) in patients with nongenetic versus genetic disease.
  
  
  METHODS
  Cross-sectional and longitudinal clinical data were collected from 231 patients with CNS/SRNS treated at eight university pediatric nephrology units with a median observation time of 113 months (interquartile range, 50-178). Genotyping was performed systematically in all patients.
  
  
  RESULTS
  The overall mutation detection rate was high at 57% (97% in CNS and 41% in SRNS); 85% of all mutations were identified by the analysis of three single genes only (NPHS1, NPHS2, and WT1), accounting for 92% of all mutations in patients with CNS and 79% of all mutations in patients with SRNS. Remission of the disease in nongenetic SRNS was observed in 78% of patients after a median treatment period of 2.5 months; 82% of nongenetic patients responded within 6 months of therapy, and 98% of patients with nongenetic SRNS and CsA-induced complete remission (normalbuminemia and no proteinuria) maintained a normal renal function. Genetic SRNS, on the contrary, is associated with a high rate of ESRD in 66% of patients. Only 3% of patients with genetic SRNS experienced a complete remission and 16% of patients with genetic SRNS experienced a partial remission after CsA therapy.
  
  
  CONCLUSIONS
  The efficacy of CsA is high in nonhereditary SRNS, with an excellent prognosis of renal function in the large majority of patients. CsA should be given for a minimum period of 6 months in these patients with nongenetic SRNS. In genetic SRNS, response to CsA was low and restricted to exceptional patients.
authors.affiliation: Pediatric Nephrology, Pediatrics II, University of Duisburg-Essen, Essen, Germany;
authors.forename: Anja K
authors.initials: AK
authors.lastname: Büscher
authors.affiliation: Institute of Human Genetics, University of Cologne, Cologne, Germany;
authors.forename: Bodo B
authors.initials: BB
authors.lastname: Beck
authors.affiliation: Pediatric Nephrology, Hanover Medical School, Hanover, Germany;
authors.forename: Anette
authors.initials: A
authors.lastname: Melk
authors.affiliation: Center for Human Genetics and Laboratory Medicine Dr. Klein, Dr. Rost and Colleagues, Martinsried, Germany;
authors.forename: Julia
authors.initials: J
authors.lastname: Hoefele
authors.affiliation: Pediatric Nephrology, University Children's Hospital, Munster, Germany;
authors.forename: Birgitta
authors.initials: B
authors.lastname: Kranz
authors.affiliation: Institute of Human Genetics, University of Cologne, Cologne, Germany;
authors.forename: Daniel
authors.initials: D
authors.lastname: Bamborschke
authors.affiliation: Pediatric Nephrology, Hanover Medical School, Hanover, Germany;
authors.forename: Sabrina
authors.initials: S
authors.lastname: Baig
authors.affiliation: Pediatric Nephrology, Ludwig-Maximilians-University Munich, Munich, Germany;
authors.forename: Bärbel
authors.initials: B
authors.lastname: Lange-Sperandio
authors.affiliation: Pediatric Nephrology, University Children's Hospital Innsbruck, Innsbruck, Austria;
authors.forename: Theresa
authors.initials: T
authors.lastname: Jungraithmayr
authors.affiliation: Pediatric Nephrology, University Children's Hospital Cologne, Cologne, Germany;
authors.forename: Lutz T
authors.initials: LT
authors.lastname: Weber
authors.affiliation: Pediatric Nephrology, University Children´s Hospital Hamburg, Hamburg, Germany; and.
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Kemper
authors.affiliation: Department of Pediatric Nephrology, University Children's Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Burkhard
authors.initials: B
authors.lastname: Tönshoff
authors.affiliation: Pediatric Nephrology, Pediatrics II, University of Duisburg-Essen, Essen, Germany;
authors.forename: Peter F
authors.initials: PF
authors.lastname: Hoyer
authors.affiliation: Pediatric Nephrology, University Children's Hospital, Munster, Germany;
authors.forename: Martin
authors.initials: M
authors.lastname: Konrad
authors.affiliation: Pediatric Nephrology, Pediatrics II, University of Duisburg-Essen, Essen, Germany; stefanie.weber@uk-essen.de.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Weber
mesh_terms: D000293:Adolescent; D001317:Austria; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease; D005858:Germany; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007223:Infant; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007668:Kidney / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000235:genetics; D008137:Longitudinal Studies; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D009154:Mutation; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D020127:Recovery of Function; D012074:Remission Induction; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D025721:WT1 Proteins / Q000235:genetics
chemical_list: D007166:Immunosuppressive Agents; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D025721:WT1 Proteins; C583751:WT1 protein, human; C113267:nephrin; D016572:Cyclosporine
keywords: FSGS; NPHS1; NPHS2; WT1; cyclosporine A; humans; kidney failure, chronic; mutation; steroid resistant nephrotic syndrome