Immunostaining findings in IgA nephropathy: correlation with histology and clinical outcome in the Oxford classification patient cohort

Background. IgA nephropathy is defined by the presence of IgA-dominant glomerular deposits. Within this definition, there is variation in the location of IgA and the presence of other immunoglobulins. The Oxford classification of IgA nephropathy identifies four histological features that are independent predictors of clinical outcome but does not include immunostains. Here, we investigate the potential clinical significance of immunostaining data. Methods. Original biopsy reports from the patients in the Oxford classification study were reviewed. The location of IgA deposits (mesangial versus mesangial + capillary wall) and the presence of IgG > trace were correlated with histological and clinical features. Results. Original biopsy reports were available for 211 of 265 patients in the Oxford classification cohort, of which 175 included sufficient details to subclassify immunostaining findings. The presence of capillary wall IgA deposits was associated with a higher mesangial cellularity score (1.3 +/- 0.6 versus 0.9 +/- 0.5 for mesangial-only IgA, P = 0.007) and endocapillary proliferation (per cent of patients with any endocapillary proliferation of 62 versus 35% for mesangial-only IgA, P = 0.01). Similarly, the presence of IgG was associated with a higher mesangial cellularity score (1.2 +/- 0.6 versus 0.9 +/- 0.5, P - 0.03) and endocapillary proliferation (per cent of patients with endocapillary proliferation of 57 versus 31% with no IgG, P = 0.009). There was no significant association between the location of IgA or the presence of IgG and rate of loss of renal function and association between the location of IgA and renal survival although patients with these immunofluorescence findings tended to receive more immunosuppression. There was a trend towards poorer renal survival in those patients with glomerular IgG (hazard ratio of 2.1, 95% confidence interval, 1.0-4.6, P = 0.06). Conclusions. We conclude that the location of glomerular IgA and the presence of IgG correlate with mesangial and endocapillary cellularity. This supports the role of IgG and capillary wall IgA in the development of proliferative changes in IgA nephropathy.