Toxic Occupational Exposures and Membranous Nephropathy

Abstract

Background and objectives: Membranous 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, & measurements: In 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.

Results: Patients 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.

Conclusions: Patients 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.

Podcast: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_10_25_CJN02930322.mp3.

Keywords: membranous nephropathy; nephrotic syndrome; occupational exposure.

Graphical abstract

Figure 1.

Comparison of the main job categories between patients with membranous nephropathy and the general population of French workers. The data source for French workers is the French National Institute of Statistics and Economic Studies 2018 and covers 26,734,000 individuals. Individuals who have never worked were not included in the analysis. Patients with membranous nephropathy worked significantly more in the construction (P<0.001) and agricultural sectors (P=0.04) and less in the service sector (P<0.001) than the general population of French workers. Statistical significance was determined by a chi-squared test or a Fisher exact test according to patient sample size. There were no missing data.

Figure 2.

Comparison of (A) lifetime and (B) 2017 prevalence of occupational exposure between patients with membranous nephropathy and the general population of French workers. The data source for French workers is the 2017 French Medical Surveillance of Employees’ Exposure to Occupational Risks survey, which is a national survey of occupational exposures developed by the French Ministry of Labor that reported the proportion of workers exposed to toxic agents among the employed population between April 2016 and September 2017. Patients with membranous nephropathy were more frequently exposed to lead, asbestos, and organic solvents during their professional activity than the general population of French workers. Statistical significance was determined by a chi-squared test or a Fisher exact test according to patient sample size. There were no missing data.

Figure 3.

Sex ratio by toxic occupational exposure to (A) organic solvents, (B) asbestos, and (C) lead. Patients with membranous nephropathy exposed to occupational toxic substances seemed to be more often men than women: organic solvents (80% men in exposed patients versus 41% men in unexposed patients, P<0.001), asbestos (90% men in exposed patients versus 55% men in unexposed patients, P=0.004), and lead (85% men in exposed patients versus 59% men in unexposed patients, P=0.12). Statistical significance was determined by a chi-squared test or a Fisher exact test according to patient sample size. There were no missing data.

Figure 4.

IL-17A levels secreted by immune cells after in vitro stimulation. Immune cells were stimulated at 37°C for 24 hours in whole blood with anti-CD3 agonist mAbs and a Toll-like receptor 7/8 agonist. IL-17A levels were measured in cellular supernatants. Statistical significance of the differences between job categories was assessed using the Mann–Whitney U nonparametric test. **P=0.01.