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Exposure to certain environmental chemicals may hinder kidney functioning, researchers reported from a systematic literature review.

The analysis by John Stanifer, MD, of Duke University in Durham, N.C., and colleagues of 74 studies pointed to a link between perfluoroalkyl and polyfluoroalkyl substances (PFASs) and poor kidney health, according to their report in the ,

Exposure to PFASs -- chemicals with ties to endocrine-disrupting properties found in everyday household items such as nonstick cookware and flame-retardants -- was also associated with alterations and disruptions in multiple pathways related to kidney disease, seen in several of the review's studies. Among the literature included, the majority were toxicological studies including both human and animal data; data from human epidemiologic studies and human pharmacokinetic analyses were also included.

As for some of the epidemiologic studies reviewed, several reported a significant association between PFAS exposure with poorer overall kidney health in humans, marked by a significant link between PFAS exposure with a lower estimated glomerular filtration rate and a higher prevalence of chronic kidney disease. This relationship was also seen in children, although only two studies involving children were included.

On a cellular level, many of these studies found kidney-related pathway alterations, some of which included disruptions in peroxisome proliferators-activated receptor (PPAR) pathways, oxidative stress pathways, dysregulation in PPARα and PPARγ, greater endothelial permeability from actin filament modeling, de-differentiation of kidney tubular epithelial cells with partial epithelial mesenchymal transition, and upregulations of NF-E2-related factor 2 pathways.

Stanifer told 番茄社区app that he was surprised to find this amount of evidence supporting the link between PFAS exposure and kidney disease: "While the epidemiological studies provided conflicting evidence that mostly but not overwhelmingly pointed toward an association, the toxicology and pharmacokinetic studies demonstrated several key mechanisms that could explain how these chemicals cause kidney disease," he said, referencing all the cellular pathways highlighted in the literature.

"It was also very interesting to learn that these compounds are taken up by the very same proximal tubule transporters that several known nephrotoxic drugs are taken up, including most notably the herb aristolochic acid which was of course responsible for the that perplexed everyone for so long."

Despite the data already available, many gaps still persist when it comes to fully understanding all the potential effects related to PFAS exposure. "The biggest [gaps] to me are that there are literally thousands of these compounds, with only slight chemical variations, which are done purposefully by the companies making them so that detection and regulation remains challenging," Stanifer explained, adding that many of these alternative chemicals are still under proprietary aegis, preventing research on them.

Other gaps that still need filling, he said, include that lack of long-term epidemiologic studies in children and adolescents, especially since those groups often have the greatest amount of exposures.

"In the context of kidney disease, these are like so many other environmental toxins in that we don't know how they interact to worsen or augment kidney disease in people with other risk factors such as diabetes or hypertension," Stanifer concluded, adding that further research in this area might also be able to shed light on how environmental chemicals can act as a driver of health disparities with kidney disease development and outcomes.

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