The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility

Abstract

Pathological classifications in current use for the assessment of glomerular disease have been typically opinion-based and built on the expert assumptions of renal pathologists about lesions historically thought to be relevant to prognosis. Here we develop a unique approach for the pathological classification of a glomerular disease, IgA nephropathy, in which renal pathologists first undertook extensive iterative work to define pathologic variables with acceptable inter-observer reproducibility. Where groups of such features closely correlated, variables were further selected on the basis of least susceptibility to sampling error and ease of scoring in routine practice. This process identified six pathologic variables that could then be used to interrogate prognostic significance independent of the clinical data in IgA nephropathy (described in the accompanying article). These variables were (1) mesangial cellularity score; percentage of glomeruli showing (2) segmental sclerosis, (3) endocapillary hypercellularity, or (4) cellular/fibrocellular crescents; (5) percentage of interstitial fibrosis/tubular atrophy; and finally (6) arteriosclerosis score. Results for interobserver reproducibility of individual pathological features are likely applicable to other glomerulonephritides, but it is not known if the correlations between variables depend on the specific type of glomerular pathobiology. Variables identified in this study withstood rigorous pathology review and statistical testing and we recommend that they become a necessary part of pathology reports for IgA nephropathy. Our methodology, translating a strong evidence-based dataset into a working format, is a model for developing classifications of other types of renal disease.

Glomerular IgG deposition predicts renal outcome in patients with IgA nephropathy

“…15,16 However, this classification does not include immunostaining patterns in the analysis. There have been several studies showing that immunofluorescent findings are related to histological severity.…”

“…13,14 The Oxford-MEST classification of IgA nephropathy identifies four types of lesions as specific pathological features that may act as independent predictors of clinical outcomes: mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T). 15,16 However, this new classification does not include immunofluorescence patterns, which might reflect the pathophysiological mechanisms active in IgA nephropathy. Our aim was to investigate the prognostic significance of glomerular IgG deposition in patients with IgA nephropathy; thus in the present study, we incorporated glomerular IgG deposits into the Oxford-MEST classification and investigated its prognostic value.…”

Renal Allograft Fibrosis: Biology and Therapeutic Targets

“…Tubulointerstitial fibrosis is the final common pathway of most progressive renal diseases and the most potent predictor of outcome (1)(2)(3)(4). In renal allografts, tubulointerstitial fibrosis is jointly assessed with tubular atrophy, given that the two almost inevitably occur in parallel, and is termed ''interstitial fibrosis/tubular atrophy (IF/TA)'' (5).…”

Selective Stimulation of VEGFR2 Accelerates Progressive Renal Disease

“…Mesangiolysis was determined as presence of dissolution of the mesangial matrix. 24 Mesangial cell number was quantified using the Oxford classification, 27 in which each glomerulus is assessed by the most cellular mesangial area, omitting the mesangial area immediately adjacent to the vascular stalk. In addition, capillary lumen number per glomerulus was also counted, to evaluate angiogenic responses.…”