Validation Study of Oxford Classification of IgA Nephropathy: The Significance of Extracapillary Proliferation

Background and objectives The Oxford classification of IgA nephropathy (IgAN) includes mesangial hyper-cellularity, endocapillary hypercellularity, segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T) as prognosticators. The value of extracapillary proliferation (Ex) was not addressed. Because the Oxford classification excludes patients with urinary protein <0.5 g/d and eGFR <30 ml/min per 1.73 m(2) at biopsy, the significance of Ex should be confirmed by validation cohorts that include more rapidly progressive cases. We present such a study. Design, setting, participants, & measurements The significance of pathologic features for development end-stage renal failure (ESRF) was examined by multivariate analysis in 702 patients with IgAN. The association of Ex with kidney survival was examined by univariate analysis in 416 patients who met the Oxford criteria and 286 who did not, separately. Results In a multivariate model, S and T were significantly associated with ESRF. With addition of Ex, not S but Ex was significant for ESRF. In univariate analysis, kidney survival was significantly lower in patients with Ex than in those without, in patients who did not meet the Oxford criteria, but such a difference was not found in patients who met it. Conclusions The prognostic significance of Ex was evident in our cohort. It seems that Ex did not emerge from the Oxford classification as a prognosticator because of exclusion of severe cases (eGFR <30 ml/min per 1.73 m2). We suggest that extracapillary proliferation be included in the next version of the Oxford classification of IgAN to widen the scope of the classification. Clin J Am Soc Nephrol 6: 2806-2813, 2011. doi: 10.2215/CJN.02890311