The impact of sex in primary glomerulonephritis

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.