title: Validation of a newly proposed histopathological classification in Japanese patients with anti-neutrophil cytoplasmic antibody-associated glomerulonephritis.
abstract: BACKGROUND
  A new histopathological classification of anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis was recently proposed. We evaluated the predictive value of this classification for renal outcome in Japanese patients.
  
  
  METHODS
  We enrolled 122 patients with ANCA-associated glomerulonephritis diagnosed at several institutions in Japan between January 2000 and March 2010. Twenty patients were excluded because of observation durations of <1 year, and/or because their biopsy specimens contained <10 glomeruli. Renal biopsy specimens were categorized into four classes according to the proposed classification. We evaluated the predictive value of immunohistochemical staining for α-smooth muscle actin (SMA), Wilm's tumor 1 (WT1), CD68, and cytokeratin for end-stage renal disease (ESRD).
  
  
  RESULTS
  The study population included 54 men and 48 women. Age, estimated glomerular filtration rate (eGFR), and proteinuria were 66.3 ± 11.3 years, 21.6 ml/min. and 1.10 g/24 h, respectively. Eighty-six patients were positive for myeloperoxidase-ANCA, five were positive for proteinase 3-ANCA, and 11 were negative for both antibodies. Median follow-up time was 41.0 months. Twenty-three patients (22.5%) developed ESRD during the follow-up period. Twelve patients died during follow up; 7/12 patients developed ESRD before death, and 5/12 patients died without ESRD. The incidence of ESRD increased with sequential categories: focal, 2/46 (4.3%); crescentic, 9/32 (28%); mixed, 8/18 (44%); and sclerotic, 4/6 (67%). The focal class had the best renal survival and the sclerotic class had the worst renal survival (p < 0.001). Kaplan-Meier renal survival analysis was similar to that of the new classification system proposal. In the multivariate analysis, the classification system tended to be a prognostic factor for ESRD (p = 0.0686, crescentic, mixed and sclerotic vs. focal, hazard ratio (HR) [95% confidence interval, CI]; 2.99 [0.61-22.7], 5.04 [1.11-36.4] and 9.93 [1.53-85.7], respectively). α-SMA-positivity also tended to be associated with ESRD (p = 0.1074).
  
  
  CONCLUSIONS
  The new histopathological classification was associated with eGFR at 1 year and tended to be associated with ESRD in our Japanese cohort with ANCA-associated glomerulonephritis. α-SMA positivity might be an additional prognostic factor for ESRD.
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwakiri
authors.forename: Shouichi
authors.initials: S
authors.lastname: Fujimoto
authors.forename: Kiyoki
authors.initials: K
authors.lastname: Kitagawa
authors.forename: Kengo
authors.initials: K
authors.lastname: Furuichi
authors.forename: Junya
authors.initials: J
authors.lastname: Yamahana
authors.forename: Yunosuke
authors.initials: Y
authors.lastname: Matsuura
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamashita
authors.forename: Shigehiro
authors.initials: S
authors.lastname: Uezono
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Shimao
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hisanaga
authors.forename: Takeshi
authors.initials: T
authors.lastname: Tokura
authors.forename: Takashi
authors.initials: T
authors.lastname: Wada
authors.forename: Kazuo
authors.initials: K
authors.lastname: Kitamura
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Asada
mesh_terms: D000368:Aged; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000097:blood / Q000145:classification*; D044466:Asian People; D005260:Female; D005500:Follow-Up Studies; D005921:Glomerulonephritis / Q000097:blood / Q000145:classification* / Q000175:diagnosis*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000145:classification / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic