Nephrotoxicity of Phthalates: A Review Based on Epidemiological and Toxicological Evidence

Phthalates are a widely used class of plasticizers known to cause various health issues. Although numerous review articles have addressed the multi-organ toxicities of Phthalates and their metabolites, a specialized review focusing on their nephrotoxicity remains scarce. In this study, the nephrotoxicity of Phthalates and their metabolites is summarized from the views of epidemiological and toxicological evidence. Epidemiological studies have demonstrated a correlation between Phthalate exposure and abnormal urinary albumin-to-creatinine ratio (ACR) as well as glomerular filtration rate (eGFR) in children. In contrast, for adults, the epidemiological evidence for the association between Phthalates and ACR/eGFR remains controversial, necessitating further investigation. In this review, we explore the potential mechanisms by which Phthalates and their metabolites may induce nephrotoxicity. These mechanisms include the following: (1) induction of oxidative stress in renal cells; (2) reduction in aldosterone levels; (3) dysregulation of the renin-angiotensin system; (4) activation of endoplasmic reticulum (ER) stress; (5) renal fibrosis; (6) disruption of sodium and water homeostasis; and (7) activation of the heat shock response defense system. Finally, based on the current understanding, we propose future research directions and necessary efforts to advance knowledge in this field.