Evaluation of the Oxford Classification of IgA nephropathy: a systematic review and meta-analysis

Background: The Oxford Classification of the pathology of immunoglobulin A (IgA) nephropathy, developed in 2009, is highly predictive of renal prognosis. It has been validated in different populations, but the results remain inconsistent.

Study design: Systematic review and meta-analysis.

Setting & population: Patients with biopsy-proven primary IgA nephropathy.

Selection criteria for studies: Studies assessing the Oxford Classification of IgA nephropathy published between January 2009 and December 2012 were included following systematic searching of the MEDLINE and EMBASE databases.

Predictor: 4 pathologic lesions of the Oxford Classification: mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), and tubular atrophy/interstitial fibrosis (T).

Outcome: Kidney failure defined as doubled serum creatinine level, 50% decline in estimated glomerular filtration rate, or end-stage kidney disease.

Results: 16 retrospective cohort studies with 3,893 patients and 570 kidney failure events were included. In a multivariate model, HRs for kidney failure were 0.6 (95% CI, 0.5-0.8; P < 0.001), 1.8 (95% CI, 1.4-2.4; P < 0.001), and 3.2 (95% CI, 1.8-5.6; P < 0.001) for scores of M0 (mesangial hypercellularity score ≤0.5), S1 (presence of segmental glomerulosclerosis), and T1/2 (>25% tubular atrophy/interstitial fibrosis), respectively, without evidence of heterogeneity. Pooled results showed that E lesions were not associated with kidney failure (HR, 1.4; 95% CI, 0.9-2.0; P = 0.1), with evidence of heterogeneity (I(2) = 54.1%; P = 0.01). Crescent (C) lesions were associated with kidney failure (HR, 2.3; 95% CI, 1.6-3.4; P < 0.001), with no evidence of heterogeneity (I(2) = 14.7%; P = 0.3).

Limitations: All studies were retrospective. This was not an individual-patient-data meta-analysis.

Conclusions: This study suggests that M, S, T, and C lesions, but not E lesions, are associated strongly with progression to kidney failure and thus should be included in the Oxford Classification system.