Validation of the Oxford classification of IgA nephropathy

Abstract

The Oxford classification of IgA nephropathy (IgAN) identified four pathological elements that were of prognostic value and additive to known clinical and laboratory variables in predicting patient outcome. These features are segmental glomerulosclerosis/adhesion, mesangial hypercellularity, endocapillary proliferation, and tubular atrophy/interstitial fibrosis. Here, we tested the Oxford results using an independent cohort of 187 adults and children with IgAN from 4 centers in North America by comparing the performance of the logistic regression model and the predictive value of each of the four lesions in both data sets. The cohorts had similar clinical and histological findings, presentations, and clinicopathological correlations. During follow-up, however, the North American cohort received more immunosuppressive and antihypertensive therapies. Identifying patients with a rapid decline in the rate of renal function using the logistic model from the original study in the validation data set was good (c-statistic 0.75), although less precise than in the original study (0.82). Individually, each pathological variable offered the same predictive value in both cohorts except mesangial hypercellularity, which was a weaker predictor. Thus, this North American cohort validated the Oxford IgAN classification and supports its utilization. Further studies are needed to determine the relationship to the impact of treatment and to define the value of the mesangial hypercellularity score.

Development and Validation of a Prediction Rule Using the Oxford Classification in IgA Nephropathy

“…However, their score has not been verified in an independent validation cohort. Furthermore, none of these previously published risk scores used an internationally accepted pathologic grading system, such as the Oxford classification (12,14,31). To our knowledge, our study is the first investigation attempting to develop a risk score using the Oxford classification and to verify its external validity in an independent cohort.…”

“…They identified four types of lesions as specific pathologic measures or features associated with the development of ESRD and/or halving of the eGFR: the mesangial hypercellularity score (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), and tubular atrophy/ interstitial fibrosis (T) (11). Recent findings have suggested the usefulness of this classification system for predicting kidney prognosis (13)(14)(15)(16). However, the prediction ability of the Oxford classification itself for individual kidney prognosis may be limited because of the difficulty in estimating individuals' absolute risks for future ESRD.…”

The New Histopathologic Classification of ANCA-Associated GN and Its Association with Renal Outcomes in Childhood

“…For example, when the predictive value of the Oxford classification system for IgA nephropathy was applied to children, there was inconsistent association of the pathologic criteria with renal outcomes (11)(12)(13)(14)(15). Therefore, we sought to validate this new pathologic classification of ANCA GN in cases with childhood onset and determine the association with renal outcomes.…”

Mycophenolate mofetil therapy in immunoglobulin A nephropathy: histological changes after treatment

“…The Oxford Classification of IgAN also identified four histological lesions associated with poor outcome: mesangial hypercellularity, endocapillary hypercellularity, segmental glomerulosclerosis and tubular atrophy/ interstitial fibrosis [1]. Glomerular endocapillary hypercellularity has been shown to be associated with a higher degree of proteinuria and impaired renal function at the time of biopsy, as well as a more rapid loss of kidney function, particularly in those patients who do not receive immunosuppressive therapy [17,[25][26][27]. Serial biopsies in patients who were treated with immunomodulatory treatment showed improvement in endocapillary proliferation [28,29] implying that this lesion may be amenable to immunosuppressive therapy.…”