Background and objectivesMembranous nephropathy is a rare autoimmune kidney disease whose increasing prevalence in industrialized countries pleads for the involvement of an environmental factor in the development of the disease. In addition, the predominance of men in membranous nephropathy, classically attributed to biologic or genetic differences between men and women, could also be due to different occupational exposures. To support this hypothesis, we sought to describe the toxic occupational exposures of patients with membranous nephropathy.Design, setting, participants, & measurementsIn this observational epidemiologic study, we compared the occupations and toxic occupational exposures of 100 patients with membranous nephropathy with those of the general population, consisting of two cohorts of 26,734,000 and 26,500 French workers. We then compared the characteristics of patients exposed to an occupational toxic substance with those of unexposed patients.ResultsPatients with membranous nephropathy worked more frequently in the construction sector than the general population (33% versus 7%,P<0.001). This difference remained significant by age and sex. They were also more frequently exposed to toxic substances, such as asbestos (16% versus 5%,P<0.001), lead (9% versus 1%,P<0.001), or organic solvents (37% versus 15%,P<0.001), than the general population. The predominance of men in the subgroup of patients occupationally exposed to toxic substances was not observed in unexposed individuals (organic solvents: 80% men versus 41%,P<0.001; asbestos: 90% men versus 55%,P=0.004). In addition, patients with phospholipase A2 receptor 1 (PLA2R1) epitope spreading were more frequently exposed to asbestos and organic solvents than patients without epitope spreading (32% versus 7%,P=0.02 and 74% versus 43%,P=0.02, respectively), with a dose-dependent effect.ConclusionsPatients with membranous nephropathy were more frequently exposed to certain occupational toxic substances, such as asbestos and organic solvents, than the general population. This occupational exposure was more frequent in men and in patients with PLA2R1 epitope spreading.Clinical Trial registry name and registration number:Immunopathological Analysis in a French National Cohort of Membranous Nephropathy (IHMN),NCT04326218.PodcastThis article contains a podcast athttps://www.asn-online.org/media/podcast/CJASN/2022_10_25_CJN02930322.mp3.