title: Histopathologic and clinical predictors of kidney outcomes in ANCA-associated vasculitis.
abstract: BACKGROUND
  A predictive histologic classification recently was proposed to determine the prognostic value of kidney biopsy in patients with antineutrophil cytoplasmic antibody-associated renal vasculitis (AAV).
  
  
  METHODS
  A dual-purpose retrospective observational cohort study to assess the reproducibility of the new classification and clinical variables that predict outcomes.
  
  
  METHODS
  169 consecutive patients with AAV were identified; 145 were included in the reproducibility study, and 120, in the outcomes study.
  
  
  METHODS
  Kidney biopsy specimens were classified according to the predominant glomerular lesion: focal, mixed, crescentic, and sclerotic. An assessment of tubular atrophy also was performed.
  
  
  RESULTS
  The primary outcome was time to end-stage kidney disease or all-cause mortality, modeled using Cox regression analysis.
  
  
  METHODS
  Estimated glomerular filtration rate, requirement for renal replacement therapy.
  
  
  RESULTS
  For the reproducibility study, the overall inter-rater reliability of the classification demonstrated variability among 3 histopathologists (intraclass correlation coefficient, 0.48; 95% CI, 0.38-0.57; κ statistic=0.46). Although agreement was high in the sclerotic group (κ=0.70), it was less consistent in other groups (κ=0.51, κ=0.47, and κ=0.23 for crescentic, focal, and mixed, respectively). For the clinical outcomes study, patients with sclerotic patterns of glomerular injury displayed the worst outcomes. Patients with focal (HR, 0.26; 95% CI, 0.12-0.58; P=0.001), crescentic (HR, 0.33; 95% CI, 0.16-0.69; P=0.003), and mixed (HR, 0.39; 95% CI, 0.18-0.81; P=0.01) patterns of injury had lower risk of the primary outcome. Tubular atrophy correlated with outcome, and advanced injury was associated with worse outcomes (HR, 5.9; 95% CI, 2.25-15.47; P<0.001). Level of kidney function at presentation strongly predicted outcome (HR per 10-mL/min/1.73m(2) increase in estimated glomerular filtration rate, 0.63; 95% CI, 0.46-0.81; P<0.001).
  
  
  CONCLUSIONS
  Data availability, given the retrospective nature of the study.
  
  
  CONCLUSIONS
  Reproducibility of the classification was seen only in patients with sclerotic patterns of glomerular injury. Sclerotic pattern of glomerular injury, advanced chronic interstitial injury, and decreased kidney function all predicted poor outcomes.
authors.affiliation: Center for Inflammatory Diseases, Department of Medicine, Monash Medical Center, Clayton, VIC, Australia; Department of Nephrology, Monash Medical Center, Clayton, VIC, Australia; Southern Clinical School, Monash Medical Center, Clayton, VIC, Australia.
authors.forename: Sharon L
authors.initials: SL
authors.lastname: Ford
authors.affiliation: Department of Nephrology, Monash Medical Center, Clayton, VIC, Australia; Southern Clinical School, Monash Medical Center, Clayton, VIC, Australia; Department of Epidemiology and Preventative Medicine, Monash University, Prahran, VIC, Australia.
authors.forename: Kevan R
authors.initials: KR
authors.lastname: Polkinghorne
authors.affiliation: Department of Anatomical Pathology, Monash Medical Center, Clayton, VIC, Australia.
authors.forename: Anthony
authors.initials: A
authors.lastname: Longano
authors.affiliation: Department of Anatomical Pathology, Monash Medical Center, Clayton, VIC, Australia.
authors.forename: John
authors.initials: J
authors.lastname: Dowling
authors.affiliation: Department of Anatomical Pathology, Monash Medical Center, Clayton, VIC, Australia.
authors.forename: Sukhpal
authors.initials: S
authors.lastname: Dayan
authors.affiliation: Department of Nephrology, Monash Medical Center, Clayton, VIC, Australia; Southern Clinical School, Monash Medical Center, Clayton, VIC, Australia.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Kerr
authors.affiliation: Center for Inflammatory Diseases, Department of Medicine, Monash Medical Center, Clayton, VIC, Australia; Department of Nephrology, Monash Medical Center, Clayton, VIC, Australia; Southern Clinical School, Monash Medical Center, Clayton, VIC, Australia.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Holdsworth
authors.affiliation: Center for Inflammatory Diseases, Department of Medicine, Monash Medical Center, Clayton, VIC, Australia; Department of Nephrology, Monash Medical Center, Clayton, VIC, Australia; Southern Clinical School, Monash Medical Center, Clayton, VIC, Australia.
authors.forename: A Richard
authors.initials: AR
authors.lastname: Kitching
authors.affiliation: Center for Inflammatory Diseases, Department of Medicine, Monash Medical Center, Clayton, VIC, Australia; Department of Nephrology, Monash Medical Center, Clayton, VIC, Australia; Southern Clinical School, Monash Medical Center, Clayton, VIC, Australia. Electronic address: sharon.ford@monash.edu.
authors.forename: Shaun A
authors.initials: SA
authors.lastname: Summers
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000175:diagnosis* / Q000473:pathology* / Q000628:therapy; D002648:Child; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
keywords: Antineutrophil cytoplasmic antibody–associated vasculitis; classification; clinical outcomes; end-stage kidney disease; glomerulonephritis; interstitial injury; kidney biopsy; mortality; sclerotic glomerular injury