MedicalResearch.com Interview with:
John W. Stanifer, MD MSc
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The key take home for me is that Perfluorinated Chemicals (PFAS) are a globally ubiquitous pollutant with high human exposure and concerning chemical properties that appear to be capable of kidney kidney disease through several plausible different mechanisms; yet, we know almost nothing about long term kidney health outcomes, who is at greatest risk for adverse outcomes, or which communities may be most negatively impacted.
The original impetus for the study was the discovery of GenX in the drinking water of Wilmington NC, a pollutant from a company upstream (see: https://www.newsobserver.com/news/politics-government/state-politics/article199846619.html ). It has been a huge story in NC and every day more and more is being discovered about how pervasive the pollution has become (https://www.usnews.com/news/best-states/north-carolina/articles/2017-12-05/genx-compound-now-detected-in-food-product-in-n-carolina). While this was what caught my attention, as a North Carolinian, I quickly realized that these news stories are all over the place as any quick google search will reveal towns and communities contaminated with these from truly all of the United States. As a health disparities researcher in kidney disease,
I have been studying disparate rural populations in North Carolina, including American Indians, who live in communities with exceptionally high rates of kidney disease, which does not appear to be fully explained by “traditional” risk factors alone such as diabetes, hypertension, obesity, etc. So with that context in mind, I really have begun to focus on these chemicals as potential second-hits or augmenters of kidney disease; we have been doing preliminary studies, in which we have found them in the serum of individuals from these areas, but before we can go further, we really needed to understand what all is known about them and the plausibility that they could cause kidney disease. Therefore, we conducted this comprehensive study to characterize what the potential mechanisms between these chemicals and kidney disease are and where the biggest gaps are.
MedicalResearch.com: Were you surprised by any of the findings?
Response: I was actually surprised by a few things about it. I thought that the link between these chemicals and kidney disease would be pretty weak, with very little to suggest these could be primary drivers of kidney disease. And 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, including oxidative stress pathways, peroxisome proliferators-activated receptor pathways, NF-E2– related factor 2 pathways, partial epithelial mesenchymal transition, and enhanced endothelial permeability through actin filament modeling.
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 Aristocholic Acid which was of course responsible for the Balken Endemic Nephropathy that perplexed everyone for so long.
MedicalResearch.com: What recommendations do you have for future research as a result of this work?
Response: Many gaps still exist. The biggest ones to me are that there are literally 1000s of these compounds, with only slight chemical variations, which make detection and regulation challenging. In fact most are still under proprietary aegis which prevents any type of study on them, and several of the “alternative” or “newer” PFCs (e.g. GEnX) have chemical properties that are particularly concerning, despite being marketed as “less toxic”. It is also very concerning to me that children and adolescents have the highest exposure; yet the long-term consequences are completely unknown and life-course epidemiology studies are very much needed. Finally, 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. So for example, wonder if you have diabetic nephropathy and are being exposed to these in high quantities? What does that mean for disparities in kidney disease and outcomes??
None of the authors have any disclosures with regards to this work.
John W. Stanifer, Heather M. Stapleton, Tomokazu Souma, Ashley Wittmer, Xinlu Zhao and L. Ebony Boulware
CJASN September 2018, CJN.04670418; DOI: https://doi.org/10.2215/CJN.04670418
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