Systematic Review of the Oxford Classification of IgA Nephropathy: Reproducibility and Prognostic Value

KEY POINTS: The Oxford classification of IgA nephropathy defined five features scored subjectively in renal biopsies, identified by the initials MESTC. Two large studies with independent observers showed reproducibility was moderate for T, moderate or poor for M and S, and poor for E and C. In multivariate analyses including clinical features, T was related to 58% of outcomes, with no correlation of MESTC with 24% of outcomes. BACKGROUND: The Oxford classification of IgA nephropathy defined five prognostic features scored subjectively in renal biopsies: mesangial cellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), interstitial fibrosis/tubular atrophy (T), and (fibro)cellular crescents (C). Pathological scoring systems should be reproducible and have prognostic value independently of clinical features. Reproducibility of the classification was not previously investigated in a systematic review, and the most recent systematic reviews of prognostic value were in 2017. METHODS: This systematic review followed PRISMA 2020 guidelines. MEDLINE, PUBMED, and EMBASE databases were searched using the terms “IgA nephropathy” and “Oxford.” Eligible papers applied the classification and mentioned statistical analysis of interobserver reproducibility and/or included multivariate analysis of outcomes related to individual Oxford scores and clinical features, including treatment with corticosteroids or other immunosuppressive drugs. RESULTS: There were 99 suitable papers before September 23, 2022. Of 12 papers that mentioned reproducibility, only six reported statistics for MEST/MESTC scoring. Four of these were small studies and/or had observers at the same institution. These were considered less representative of application of the classification than two large studies with independent observers, in which agreement was moderate for T, either moderate or poor for M and S, and poor for E and C. In 92 papers with 125 multivariate analyses of various outcomes, the commonest Oxford element associated with outcomes was T (73 of 125, 58%), with no correlation of any element with outcomes in 30 analyses (24%). Treatment with immunosuppression was often related to scores, particularly C and E, without consistent relations between Oxford scores and outcomes in immunosuppressed patients. CONCLUSIONS: This systematic review showed limitations of the Oxford classification in practice, particularly the moderate or poor reproducibility of scores. T was the Oxford score most often related to clinical outcomes, but even this was not consistently reliable as a prognostic indicator.