Histopathologic and clinical predictors of kidney outcomes in ANCA-associated vasculitis.

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). A dual-purpose retrospective observational cohort study to assess the reproducibility of the new classification and clinical variables that predict outcomes. 169 consecutive patients with AAV were identified; 145 were included in the reproducibility study, and 120, in the outcomes study. Kidney biopsy specimens were classified according to the predominant glomerular lesion: focal, mixed, crescentic, and sclerotic. An assessment of tubular atrophy also was performed. The primary outcome was time to end-stage kidney disease or all-cause mortality, modeled using Cox regression analysis. Estimated glomerular filtration rate, requirement for renal replacement therapy. 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). Data availability, given the retrospective nature of the study. 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.

Ford SL ，Polkinghorne KR ，Longano A ，Dowling J ，Dayan S ，Kerr PG ，Holdsworth SR ，Kitching AR ，Summers SA ... -  《-》

Validation of a histopathologic classification scheme for antineutrophil cytoplasmic antibody-associated glomerulonephritis.

Antineutrophil cytoplasmic antibody-associated small-vessel vasculitides cause multiple organ system disease including rapidly progressive glomerulonephritis. Recently, Berden et al (J Am Soc Nephrol. 2010;21:1628-1636) proposed a new histopathologic classification scheme separating renal biopsies into 4 classes: focal, crescentic, mixed, and sclerotic. We validated the prognostic implications of this classification scheme in a retrospective cohort study of 67 individuals with antineutrophil cytoplasmic antibody glomerulonephritis who underwent kidney biopsy in Calgary, Alberta, between 2005 and 2010. Their biopsies were rescored according to the classification scheme of Berden et al. Additional tubulointerstitial parameters were also scored. Clinical information including demographics and creatinine values at presentation and 1-year follow-up was retrieved. The mean age was 60 years. Forty-one percent were female. Biopsies were classified as follows: 35% crescentic, 32% mixed, 21% focal, and 11% sclerotic. Ten patients (14%) died within 1 year. Among surviving patients, the overall mean (95% confidence interval) change in estimated glomerular filtration rate (eGFR) at 1 year was 11 (7-15) mL/min per 1.73 m(2), and this change significantly differed (P = .02) between the classes: 19 (11-27) mL/min per 1.73 m(2) with crescentic histology, 11 (1-21) mL/min per 1.73 m(2) with focal, 8 (3-13) mL/min per 1.73 m(2) with mixed, and -4 (-7 to -1) mL/min per 1.73 m(2) with sclerotic. Tubulointerstitial pathology parameters did not predict outcomes. Patients with crescentic class biopsies showed significantly more improvement in eGFR at 1 year compared with the mixed (P = .04) and sclerotic (P = .005) classes. The focal class was associated with the highest eGFR values at presentation and 1 year. These findings validate the prognostic utility of the Berden classification scheme and suggest that it may be generalizable.

Nohr E ，Girard L ，James M ，Benediktsson H ... -  《-》

Predictors of Renal Outcomes in Sclerotic Class Anti-Neutrophil Cytoplasmic Antibody Glomerulonephritis.

The prognostic value of the anti-neutrophil cytoplasmic antibody (ANCA) associated glomerulonephritis (GN) classification has been demonstrated in several cohorts with sclerotic class having the worst renal outcome. Relevant published data on factors predicting outcomes in sclerotic ANCA GN is limited. Sclerotic ANCA GN patients were recruited from 5 centers worldwide for this retrospective cohort study. We describe the clinical characteristics of this cohort and evaluate predictors of 1-year glomerular filtration rate (GFR) and end-stage renal disease (ESRD). Kidney function at 12 months as measured by Modification of Diet in Renal Disease estimated GFR (eGFR) was modeled by simple and multiple linear regression analyses. We used Cox proportional hazards regression modeling to evaluate ESRD-free survival. Of the 50 patients, 92% were Caucasian and 60% male with a mean age of 61 years. While 72% had renal limited disease, 82% were MPO ANCA positive. Kidney biopsies contained a median of 20 (interquartile range [IQR] 15-34) glomeruli with 96% showing moderate to severe interstitial fibrosis. Overall, 96% of patients received immunosuppressive drug therapy and 16% received plasmapheresis. Treatment response was achieved in all but 1 patient. The median (IQR) eGFR at entry was 14.5 (9-19) mL/min/1.73 m2. Over a median (IQR) follow-up of 33.5 (17-82) months, 26 patients reached ESRD. Ten patients died with 6 of the deaths occurring within the first year of diagnosis. The hazard of progression to ESRD was significantly higher in those with lower GFR at study entry (p = 0.003) and with higher degree of tubular atrophy (p = 0.043). Renal recovery is rare among sclerotic ANCA GN patients requiring dialysis at entry and 12% of patients died in the first year. Entry GFR and tubular atrophy were significant predictors of GFR at 12 months and renal survival in patients with sclerotic class ANCA GN.

Menez S ，Hruskova Z ，Scott J ，Cormican S ，Chen M ，Salama AD ，Alasfar S ，Little MA ，Safrankova H ，Honsova E ，Tesar V ，Geetha D ... -  《-》

Prognostic Value of Histologic Classification of ANCA-Associated Glomerulonephritis.

A kidney biopsy is preferred for the diagnosis of ANCA-associated vasculitis with renal involvement. The aim of our study was to evaluate the prognostic value of a histopathologic classification scheme recently proposed by an international consortium of renal pathologists in a large Norwegian cohort. Patients diagnosed with ANCA-associated GN were included from the Norwegian Kidney Biopsy Registry 1991-2012. Renal morphology was classified as focal, mixed, crescentic, or sclerotic. Study end point was ESRD. Patients were followed from kidney biopsy to end of 2012. Two hundred fifty patients with ≥10 glomeruli in the biopsy were included in our study. During a median follow-up of 3.5 years (0.7-7.6), 60 cases of ESRD occurred. Ninety-six (38%) biopsies were classified as focal, 61 (24%) biopsies were classified as mixed, 71 (28%) biopsies were classified as crescentic, and 22 (9%) biopsies were classified as sclerotic; 1- and 5-year cumulative renal survival rates were 96% and 90%, respectively, for the focal class, 86% and 75%, respectively, for the mixed class, 81% and 69%, respectively, for the crescentic class, and 56% and 51%, respectively, for the sclerotic class. By multivariate Cox regression analyses, the sclerotic class had a significantly worse renal prognosis than the focal (hazard ratio, 9.65; 95% confidence interval, 2.38 to 39.16) or combined mixed/crescentic classes (hazard ratio, 3.27; 95% confidence interval, 1.41 to 7.61), but no significant differences in outcome were observed in the crescentic class compared with the mixed class (hazard ratio, 1.13; 95% confidence interval, 0.44 to 2.87) or the combined mixed/crescentic class compared with the focal class (hazard ratio, 1.93; 95% confidence interval, 0.61 to 6.12). Accuracy by receiver operator characteristic curve analysis was estimated to be 0.72 (95% confidence interval, 0.65 to 0.80). In 108 additional patients with three to nine glomeruli in the biopsy, the prognostic value of this classification scheme was unchanged. The histopathologic classification is a predictor of renal outcome of moderate quality. Merging the mixed and crescentic classes in the future could simplify the scheme.

Bjørneklett R ，Sriskandarajah S ，Bostad L 《-》

Re-evaluation of the histopathologic classification of ANCA-associated glomerulonephritis: a study of 121 patients in a single center.

Chang DY ，Wu LH ，Liu G ，Chen M ，Kallenberg CG ，Zhao MH ... -  《-》