Developments in the Histopathological Classification of ANCA-Associated Glomerulonephritis

Abstract

Background and objectives: The histopathologic classification for ANCA-associated GN distinguishes four classes on the basis of patterns of injury. In the original validation study, these classes were ordered by severity of kidney function loss as follows: focal, crescentic, mixed, and sclerotic. Subsequent validation studies disagreed on outcomes in the crescentic and mixed classes. This study, driven by the original investigators, provides several analyses in order to determine the current position of the histopathologic classification of ANCA-associated GN.

Design, setting, participants, & measurements: A validation study was performed with newly collected data from 145 patients from ten centers worldwide, including an analysis of interobserver agreement on the histopathologic evaluation of the kidney biopsies. This study also included a meta-analysis on previous validation studies and a validation of the recently proposed ANCA kidney risk score.

Results: The validation study showed that kidney failure at 10-year follow-up was significantly different between the histopathologic classes (P<0.001). Kidney failure at 10-year follow-up was 14% in the crescentic class versus 20% in the mixed class (P=0.98). In the meta-analysis, no significant difference in kidney failure was also observed when crescentic class was compared with mixed class (relative risk, 1.15; 95% confidence interval, 0.94 to 1.41). When we applied the ANCA kidney risk score to our cohort, kidney survival at 3 years was 100%, 96%, and 77% in the low-, medium-, and high-risk groups, respectively (P<0.001). These survival percentages are higher compared with the percentages in the original study.

Conclusions: The crescentic and mixed classes seem to have a similar prognosis, also after adjusting for differences in patient populations, treatment, and interobserver agreement. However, at this stage, we are not inclined to merge the crescentic and mixed classes because the reported confidence intervals do not exclude important differences in prognosis and because an important histopathologic distinction would be lost.

Keywords: ANCA; Antibodies; Antineutrophil Cytoplasmic; Biopsy; Cohort Studies; Confidence Intervals; Observer Variation; Prognosis; Renal Insufficiency; glomerulonephritis; kidney biopsy.

Graphical abstract

Figure 1.

Significantly different kidney survival between the histopathological classes in the validation cohort. (A) At 10-year follow-up, kidney survival was different between the four classes (log rank; P<0.001) but not between crescentic and mixed class (log rank; P=0.98). (B) When biopsies with five to ten glomeruli were excluded, kidney survival remained different between the four classes (log rank; P=0.003).

Figure 2.

Forest plots of risk ratios showing no significantly differences between crescentic and mixed classes in the meta-analyses. (A) Using kidney failure-event rates in adult patients. (B) Using adjusted hazard ratios in adult patients. (C) Using kidney failure-event rates in pediatric patients. 95% CI, 95% confidence interval; IV, inverse variance; M-H, Mantel-Haenszel; SE, SEM.

Figure 3.

Significantly different kidney survival in the validation cohort according to kidney risk score. Kidney survival was significantly different between the kidney risk groups (log rank; P<0.001).