Phthalates May Heighten Cardiovascular Risk in Patients with CKD

In a new study that deepens concerns about environmental pollutants in vulnerable populations, researchers have identified a significant link between phthalate exposure and cardiovascular disease (CVD) risk in individuals with chronic kidney disease (CKD). Drawing on over a decade of nationally representative health data, the findings suggest that common plasticizers used in medical and consumer products may be contributing to poor cardiovascular outcomes among patients already at elevated risk.

The study, published in Renal Failure, analyzed data from 2,227 CKD patients enrolled in the National Health and Nutrition Examination Survey (NHANES) between 2003 and 2018. Researchers found that higher urinary concentrations of several phthalate metabolites—including mono-n-butyl phthalate (MBP), mono-(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-carboxypentyl) phthalate (MECPP)—were consistently associated with greater odds of self-reported CVD.

Phthalates are synthetic chemicals widely used to increase the flexibility of plastics and are commonly found in food packaging, personal care products, and medical devices. For patients with CKD, the risk of exposure is especially high due to frequent medical interventions such as dialysis, which often involves phthalate-containing tubing and equipment.

To account for real-world exposure scenarios—where individuals encounter mixtures of phthalates rather than isolated compounds—the researchers employed multiple advanced statistical models, including Weighted Quantile Sum (WQS), Quantile G-Computation (qgcomp), and Bayesian Kernel Machine Regression (BKMR). All three methods converged on a consistent finding: exposure to phthalate mixtures was positively correlated with CVD risk.

One metabolite in particular, MEOHP (a byproduct of DEHP, a plasticizer commonly used in medical devices), emerged as a significant contributor across all models. Its strong association with CVD risk echoes previous research linking MEOHP to cardiovascular mortality in diabetic populations.

Beyond the epidemiologic analysis, the study integrated a network toxicology approach to explore the molecular mechanisms underlying these associations. By mapping phthalate targets and intersecting them with known CKD and CVD-related genes, the researchers identified three key proteins—PPARG, CASP9, and CTSS—as potential mediators of the toxic effects. These genes are involved in pathways related to lipid metabolism, apoptosis, inflammation, and fibrosis, all of which are central to both renal and cardiovascular disease progression.

Molecular docking simulations supported the plausibility of these interactions, showing stable binding between phthalate compounds and the encoded proteins. The study also highlighted the bidirectional regulatory effects phthalates may exert on PPARG, a nuclear receptor implicated in both atherosclerosis and renal fibrosis, suggesting a complex interplay that warrants further investigation.

Further research—particularly prospective cohort studies and clinical trials—will be needed to clarify causality and explore whether reducing phthalate exposure can improve cardiovascular outcomes in CKD. Until then, the study adds to mounting evidence that environmental pollutants may play a more central role in chronic disease than previously understood.