title: Clinico-pathological correlations of congenital and infantile nephrotic syndrome over twenty years.
abstract: BACKGROUND
  Nephrotic syndrome (NS) presenting early in life is caused by heterogeneous glomerular diseases. We retrospectively evaluated whether histological diagnosis in children presenting with NS in the first year of life predicts remission or progression to end-stage kidney disease (ESKD).
  
  
  METHODS
  This is a single centre retrospective review of all children diagnosed with NS before one year of age between 1990 and 2009. All subjects had a renal biopsy, which was independently blindly reviewed by a single renal pathologist for the purpose of this study.
  
  
  RESULTS
  Forty-nine children (25 female) who presented at 0.1-11.6 (median 1.6) months were included with 31 presenting within the first three months of life. Histopathological review diagnostic categories were; 13 Mesangial proliferative glomerulopathy (MesGN), 12 Focal and segmental glomerulosclerosis (FSGS), 11 Finnish type changes, eight Diffuse Mesangial Sclerosis (DMS), three Minimal change disease (MCD) and one each of Dense Deposit Disease (DDD) and Membranous nephropathy. Two children died from haemorrhagic complications of the biopsy. Eight children achieved remission (four MesGN, one Finnish type changes, one FSGS, one MCD and one membranous) with patient and renal survival of 73 % and 43 %, respectively, at follow-up duration of 5-222 (median 73) months (with five lost to follow-up). All children with Finnish-type histopathological changes presented within five months of age. Due to the historical nature of the cohort, genetic testing was only available for 14 children, nine of whom had an identifiable genetic basis (seven NPHS1, one PLCE1 and one ITGA3) with none of these nine children achieving remission. All of them had presented within four months of age and required renal replacement therapy, and two died.
  
  
  CONCLUSIONS
  Histopathological findings are varied in children presenting with NS early in life. Whilst groups of histological patterns of disease are associated with differing outcomes, accurate prediction of disease course in a specific case is difficult and more widespread genetic testing may improve the understanding of this group of diseases and their optimal management.
authors.affiliation: Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK, jkari@doctors.org.uk.
authors.forename: Jameela A
authors.initials: JA
authors.lastname: Kari
authors.forename: Giovanni
authors.initials: G
authors.lastname: Montini
authors.forename: Detlef
authors.initials: D
authors.lastname: Bockenhauer
authors.forename: Eileen
authors.initials: E
authors.lastname: Brennan
authors.forename: Lesley
authors.initials: L
authors.lastname: Rees
authors.forename: Richard S
authors.initials: RS
authors.lastname: Trompeter
authors.forename: Kjell
authors.initials: K
authors.lastname: Tullus
authors.forename: William
authors.initials: W
authors.lastname: Van't Hoff
authors.forename: Aoife
authors.initials: A
authors.lastname: Waters
authors.forename: Emma
authors.initials: E
authors.lastname: Ashton
authors.forename: Nicholas
authors.initials: N
authors.lastname: Lench
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Sebire
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Marks
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D001706:Biopsy / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D007668:Kidney / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000473:pathology; D008297:Male; D009154:Mutation / Q000235:genetics; D009392:Nephrectomy; D009404:Nephrotic Syndrome / Q000151:congenital* / Q000235:genetics / Q000503:physiopathology*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents