Nephrotoxic Effects of Endocrine-Disrupting Chemicals: A Systematic Review

Endocrine-disrupting chemicals (EDCs) are widespread environmental pollutants that interfere with hormonal regulation and are increasingly linked to kidney dysfunction. The kidney's central role in xenobiotic filtration and excretion makes it vulnerable to cumulative toxic exposures that trigger oxidative stress, inflammation, and apoptosis, leading to chronic kidney disease (CKD) and related disorders. This systematic review synthesized evidence from human, animal, and computational studies assessing exposure to multiple EDC classes, including bisphenols, phthalates, parabens, alkylphenols, volatile organic compounds (VOCs), per- and polyfluoroalkyl substances (PFASs), pesticides, and heavy metals, and their associations with kidney outcomes. A comprehensive search of PubMed, Scopus, Web of Science, and the Cochrane Library was conducted up to October 2025 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Methodological quality was evaluated using the AXIS tool for cross-sectional studies, the Newcastle-Ottawa Scale (NOS) for cohort and case-control studies, the Joanna Briggs Institute (JBI) checklists, and the Toxicological Data Reliability Assessment Tool (ToxRTool). Of 42,006 records screened, 10 studies met the inclusion criteria, encompassing large population cohorts, animal experiments, and molecular docking analyses. Cross-sectional datasets, such as the National Health and Nutrition Examination Survey (NHANES), demonstrated significant associations between VOCs, phthalates, and heavy metals (particularly lead and cadmium) and increased CKD and diabetic kidney disease (DKD) risk, while some PFASs showed neutral or inverse associations. Experimental evidence confirmed that bisphenol and alkylphenol derivatives induce renal injury via oxidative stress, p53 activation, and apoptosis, and dialysis-related studies revealed iatrogenic bisphenol contamination. Overall, these findings highlight the kidney's susceptibility to environmental toxicants and emphasize the need for stricter regulation of EDC-containing materials, improved biomonitoring of cumulative exposures, and further mechanistic research to clarify dose-response relationships and long-term renal effects.