S. Troyanov

BACKGROUND: Studies comparing the impact of sex in primary glomerular disease have reported conflicting results. METHODS: We analysed 395 membranous (MGN), 370 focal and segmental glomerulosclerosis (FSGS) and 542 IgA nephropathy patients to determine the impact of the patients' sex on outcome. We assessed initial and follow-up blood pressure, proteinuria, anti-hypertensive and immunosuppressive therapy, rate of renal function decline and survival from renal failure or a 50% decrease in creatinine clearance (combined event). RESULTS: Women accounted for one-third of the cohort. At presentation they were on average 2 years younger than men, and over follow-up received no more immunosuppression or anti-hypertensive agents than their male counterpart. Their mean arterial pressure (MAP) overall was 2 mmHg lower. Proteinuria at presentation and during follow-up in women compared to men was 50% and 30% lower in MGN and FSGS, while no differences were seen in IgA nephropathy. The rate of renal function decline and outcome favoured women over men in MGN (hazard ratios of a combined event of 0.63, 95% CI 0.40-1.00, P = 0.05) and in FSGS (HR 0.67, 95% CI 0.48-0.95, P = 0.02) but not in IgA nephropathy. These differences were not independent of blood pressure and proteinuria, indicating that these sex-dependent risk factors accounted for most of the hazards seen in men. However, the quantitative effect of proteinuria on the rate of progression was distinct and modified by sex in MGN and FSGS with higher proteinuria levels having less impact on progression rate in women. This interaction was independent of blood pressure. CONCLUSIONS: Women have a better outcome than men in MGN and FSGS but not in IgA nephropathy. These benefits are mostly mediated through both lower proteinuria and blood pressure at presentation and throughout follow-up, although females did have an independent advantage at higher levels of proteinuria.

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.