title: The new histopathologic classification of ANCA-associated GN and its association with renal outcomes in childhood.
abstract: OBJECTIVE
  A proposed histopathologic classification for ANCA-associated GN is predictive of long-term renal outcome in adult populations. This study sought to validate this system in a pediatric cohort.
  
  
  METHODS
  This was a retrospective, single-center, cohort study of 40 children diagnosed and followed until their transition to adult care at one institution between 1987 and 2012. Renal biopsy specimens were reviewed by a pathologist blinded to patient outcome and were classified using the new histopathologic classification system of focal, crescentic, mixed, and sclerotic groups. Time to the composite outcome of CKD stages 3 and 4 (determined by eGFR with repeated creatinine measures using the Schwartz equation) or ESRD (defined as dialysis dependence or transplantation) were ascertained.
  
  
  RESULTS
  The study population consisted of 40 children (70% female), followed for a median of 2.4 years. The biopsy specimens were categorized as focal in 13 patients (32.5%), crescentic in 20 (50%), mixed in two (5%), and sclerotic in five (12.5%). Mixed and crescentic were combined for analyses. Survival analysis of time to the composite renal endpoint of at least 3 months of eGFR<60 ml/min per 1.73 m(2) or ESRD differed significantly among the three biopsy groups log-rank P<0.001), with an adjusted hazard ratio of 3.14 (95% confidence interval, 0.68 to 14.4) in the crescentic/mixed group and 23.6 (95% confidence interval, 3.9 to 144.2) in the sclerotic category compared with the focal category. The probability of having an eGFR>60 ml/min per 1.73 m(2) at 2 years was 100% for the focal, 56.5% for the crescentic/mixed, and 0% for the sclerotic biopsy categories.
  
  
  CONCLUSIONS
  This study showed the clinical utility of this histopathologic classification system and its ability to discriminate renal outcomes among children with ANCA GN.
authors.affiliation: Divisions of Nephrology.
authors.forename: Damien G
authors.initials: DG
authors.lastname: Noone
authors.affiliation: Rheumatology, and.
authors.forename: Marinka
authors.initials: M
authors.lastname: Twilt
authors.affiliation: Divisions of Nephrology.
authors.forename: Wesley N
authors.initials: WN
authors.lastname: Hayes
authors.affiliation: Pathology, The Research Institute, and Department of Pathobiology and Laboratory Medicine and.
authors.forename: Paul S
authors.initials: PS
authors.lastname: Thorner
authors.affiliation: Rheumatology, and The Research Institute, and Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Susanne
authors.initials: S
authors.lastname: Benseler
authors.affiliation: Rheumatology, and Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Ronald M
authors.initials: RM
authors.lastname: Laxer
authors.affiliation: Divisions of Nephrology, The Research Institute, and Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto, Ontario, Canada, and rulan.parekh@sickkids.ca.
authors.forename: Rulan S
authors.initials: RS
authors.lastname: Parekh
authors.affiliation: Divisions of Nephrology, Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Diane
authors.initials: D
authors.lastname: Hebert
mesh_terms: D000293:Adolescent; D000367:Age Factors; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology*; D001706:Biopsy; D002648:Child; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D005921:Glomerulonephritis / Q000145:classification / Q000276:immunology* / Q000401:mortality / Q000473:pathology* / Q000503:physiopathology / Q000628:therapy; D005923:Glomerulosclerosis, Focal Segmental / Q000276:immunology / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D007668:Kidney / Q000276:immunology* / Q000473:pathology* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000473:pathology; D008297:Male; D009864:Ontario; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D051436:Renal Insufficiency, Chronic / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic
keywords: ANCA; glomerulonephritis; pediatric nephrology; renal biopsy; vasculitis