Sex differences in epidemiology and clinical presentation of glomerular diseases in a nationwide Spanish biopsy registry

Abstract

Sex differences influence the epidemiology and clinical expression of kidney diseases. Most primary glomerulonephritis shows male predominance, whereas lupus nephritis remains strongly female-biased. Large national cohorts with sex-stratified analyses are limited. We analysed all native kidney biopsies performed between 1994 and 2024 and recorded in the Spanish Registry of Glomerulonephritis (n = 34,258). All biopsies were evaluated using light microscopy and direct immunofluorescence; electron microscopy was added when required. Patients were stratified by sex, age (< 16, 45–64, 65–74, > 74 years), and study period (six-year intervals). Clinical presentations and major histological diagnoses were compared between sexes. Men accounted for 59.9% of biopsies, with stable predominance across all periods. Men presented with higher serum creatinine, lower creatinine clearance, and greater proteinuria. Women more frequently exhibited asymptomatic urinary abnormalities, whereas men more often had chronic kidney disease at diagnosis. AUA occurred in 25% of women vs 19% of men, while CKD was present in 17% of men vs 12% of women (p < 0.001). Sex-specific patterns were observed across major diagnoses. Young women were more frequently represented in IgA nephropathy and podocytopathies; women with membranous nephropathy were more common in both the pediatric and the oldest age groups; men with lupus nephritis presented with more aggressive clinical syndromes; and women with ANCA-associated vasculitis were biopsied with higher proteinuria and worse renal function. This nationwide biopsy-based registry demonstrates persistent male predominance in glomerular diseases but reveals important sex-specific differences in age distribution and clinical presentation. Incorporating sex-stratified analyses into registries and clinical studies is essential to improve diagnostic accuracy and guide personalized nephrology.