Perfluorinated Chemicals as Emerging Environmental Threats to Kidney Health

MedicalResearch.com Interview with:
John W. Stanifer, MD MSc
Duke Health

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.

 

Citation:

Perfluorinated Chemicals as Emerging Environmental Threats to Kidney Health
A Scoping Review

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 

[last-modified] 

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Microwave Radiation Targeting Diplomats in Cuba and China Resembles Traumatic Brain Injury

MedicalResearch.com Interview with:

Beatrice Golomb, MD, PhD Director of the Golomb Research Group Professor of Medicine University of California, San Diego

Dr. Golomb

Beatrice Golomb, MD, PhD
Director of the Golomb Research Group
Professor of Medicine
University of California, San DiegoResponse:

MedicalResearch.com: What is the background for this study? How was the radiation emitted?

Response: Possibilities include surveillance devices (or things to jam them), electronic weapons, or, less likely, “innocent” communications devices.


MedicalResearch.com: What are the main findings?

Response: That all key features of diplomats’ experiences comport with pulsed radiofrequency/ microwave (RF/MW) radiation.

  1. The nature of the “sounds” heard – chirping, clicking, ringing, grinding/buzzing – are known “sounds” produced via the “microwave auditory effect” aka Frey effect.  Different sounds are heard by different people, because the character of the sound heard depends on head dimensions (as well as pulse characteristics). Sounds were primarily heard at night: consistent with the microwave auditory effect, which requires low ambient noise. Some diplomats reported that sounds were spatially localized with “laserlike” specificity – said to defy known physics. This defies the physics of sound, but not radiation. The “sound” was reported to follow a diplomat as he walked, within the territory in which it was heard. Sound from a fixed source does not seem to follow people – but the microwave auditory affect does, often perceived as being located just behind (or in some cases just above, or inside) the head of the person, irrespective of the person’s orientation relative to the radiation source.
  2. The symptoms reported following these experiences also fit. Rates of reported symptoms in diplomats – headache, cognitive and sleep problems dominating, then dizziness, tinnitus, anxiety, nausea at lesser but still high rates – match closely with rates of the same symptoms reported in a 2012 Japanese study of people who report health effects from radiation, typically including pulsed RF/MW. Hearing loss is a relatively distinctive and prominent symptom in both diplomats, and RF/MW affected civilians. In both groups, some reportedly experience speech problems, balance problems, nosebleed, and strange sensations of vibration and pressure.

Reports of symptoms with RF/MW exposures date at least to the 1920s, affecting radio amateurs and shipboard radio operators as well as others working with radar or microwaves in occupational settings. By 1971/72, a Naval report with over 2300 citations (many from Russia and Eastern Europe), assessing effects of low intensity RF radiation, had whole sections devoted to each of a number of the symptoms diplomats report.

  1. Hundreds (if not thousands) of studies have illuminated mechanisms by which these effects may arise, centered on oxidative stress (the kind of injury that antioxidants help to defend against) – and many downstream effects of oxidative stress (membrane damage, blood brain barrier impairment with potential for brain swelling, inflammation, voltage gated calcium (and other) channel effects (which can also lead to oxidative stress), mitochondrial impairment, autoimmune activation, etc.)

Affected persons are a minority (in both settings), and in the nondiplomat setting, vulnerability has been tied to genetic variants less adept at defending against oxidative stress; and low concentrations of a critical antioxidant. In both groups, brain imaging studies resemble traumatic brain injury; and in both, at least some of those affected had prior head injury. Head injury may be a predisposing factor, as well as possible consequence.

Reprising findings also shown for research on other lucrative products with potential to cause harm in some, there is a powerful tie between study results and financial conflict of interest (e.g. source of study funding or conflicts by authors).

  1. There is precedent for use of microwaves in the diplomat setting. It is known that the US embassy in Moscow was microwaved for several decades beginning in the early 1950s (with some embassy staff citing – disputed – health problems). A 1976 NY Times story (“Moscow rays linked to U.S. bugging”) referenced speculation these were for surveillance; the Soviets claimed their purpose was to thwart U.S. listening devices on the roof of the embassy.

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Interventions Reduced Childhood Lead Levels, But Did Not Improve Neurobehavioral Outcomes

MedicalResearch.com Interview with:

Joseph M. Braun, MSPH, PhD  Associate Professor of Epidemiology Epidemiology Master's Program Director  Brown University School of Public Health

Dr. Braun

Joseph M. Braun, MSPH, PhD
Associate Professor of Epidemiology
Epidemiology Master’s Program Director
Brown University School of Public Health

MedicalResearch.com: What is the background for this study?

Response: Childhood lead poisoning continues to be a problem in the United States and residential lead hazards are the major source of Pb exposure in young children. However, no studies have attempted to prevent exposure to lead hazards through primary prevention. Thus, we randomized 355 pregnant women to a comprehensive residential intervention and followed their children for up to 8 years to determine if childhood lead poisoning and associated cognitive deficits and behavior problems can be prevented.

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More Evidence UV Filters in Sunscreens Affect Marine Life

MedicalResearch.com Interview with:
sunscreen creative commonsAdela J. Li, PhD

Research Affiliate
Wadsworth Center, Rm. D597
New York State Dept. of Health
Empire State Plaza
Albany, NY, 12201-0509
On the behalf of Dr. Kelvin Leung 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Most people love the beach. In order to block the sun’s damaging UV radiation, people generally slather on a thick layer of sunscreen against sunburn and skin cancer. Sunscreen is suggested to be re-applied every few hours regarding its effectiveness as well as being washed off into the water. These UV filters have been detected in the environment but most studies concluded that individual sunscreen chemicals pose no/low risk to animals or human. However, UV filters constitute a heterogeneous group of chemicals in sunscreens. We are wondering if combination of UV filters would induce higher toxicity than individual compounds, and whether these chemical interactions would develop over time, becoming increasingly dangerous to the living systems.

Our study found seven of the nine UV filters in Shenzhen waters, China — a rapidly urbanized city with over 20 popular recreational beaches, surprisingly, a reservoir and tap water. After exposing artemia to three dominant UV filters and then feeding these artemia to zebrafish adults, concentrations in both were up to 4 times higher when exposed to the mixtures than when exposed to only a single UV filter. A short-term of 25-day dietary exposure to the zebrafish adults did not appear to significantly influence early life stage development of the second generation; however, relatively long exposure over 47 days had significant adverse effects on embryo development. Continue reading

Triclosan in Personal Care Products Can Induce Antibiotic Resistance

MedicalResearch.com Interview with:

Dr Jianhua Guo PhD ARC Future Fellow, Senior Research Fellow Advanced Water Management Centre University of Queensland Brisbane Australia

Dr. Jianhua Guo

Dr Jianhua Guo PhD
ARC Future Fellow, Senior Research Fellow
Advanced Water Management Centre
University of Queensland
Brisbane Australia

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: It was found that wastewater from residential areas has similar or even higher levels of antibiotic resistant bacteria and antibiotic resistance genes compared to hospitals, where you would expect greater antibiotic concentrations. Thus, we wonder whether non-antibiotic chemicals such as triclosan can directly induce antibiotic resistance, because triclosan could be ubiquitously detected in various water environments, like wastewater.

We found triclosan found in personal care products that we use daily could directly induce multi-drug resistance through mutation. The discovery should be a wake-up call to re-evaluate the potential impact of non-antibiotic chemicals on the dissemination of antibiotic resistance.

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Animal Model Suggests BPA May Have Multigenerational Effect On Communication Patterns

MedicalResearch.com Interview with:

Cheryl Rosenfeld PhD DVS Professor of biomedical sciences in the College of Veterinary Medicine investigator in the Bond Life Sciences Center, and  research faculty member for the Thompson Center for Autism and Neurobehavioral Disorders University of Missouri

Dr. Rosenfeld

Cheryl Rosenfeld PhD DVS
Professor of biomedical sciences in the College of Veterinary Medicine
investigator in the Bond Life Sciences Center, and
research faculty member for the Thompson Center for Autism and Neurobehavioral Disorders
University of Missouri

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: My laboratory has been examining the effects of developmental exposure to the endocrine disrupting chemical (EDC), bisphenol A (BPA) on later neurobehavioral responses in a variety of rodent models, including California mice. This species is unique in that both parents rear the pups and they have monogamous social structure, similar to most human societies.

We had previously found that developmental exposure to BPA or another EDC, ethinyl estradiol (EE), disrupted later maternal and paternal care by F1 offspringto their F2 pups. Rodent pups use vocalizations both in the range of human hearing (20,000 hertz or below) and outside of the range of human hearing (20,000 hertz) to communicate with each other and their parents, and for the latter, such communications serve as a trigger to provide additional parental care in the form of nutrition or warmth to the pups.

Thus, in the current studies we sought to determine if exposure of the grandparents to BPA or EE could lead to disruptions in their grandoffspring (F2 generation) pup communications that might then at least partially account for the parental neglect of their F1 parents.

We found that early on female BPA pups took longer to call to their parents but later during the neonatal period they vocalized more than pups whose grandparents were not exposed to either chemical. Such vocalization changes could be due to multigenerational exposure to BPA and/or indicate that the pups are perceiving and responding to the reduced parental care and attempting but failing to signal to their F1 parents that they need more attention.

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Air Pollution Linked To Increased Respiratory Infections in Kids

MedicalResearch.com Interview with:

Benjamin D. Horne, PhD Director of Cardiovascular and Genetic Epidemiology Intermountain Heart Institute Intermountain Medical Center Salt Lake City, Utah 

Dr. Horne

Benjamin D. Horne, PhD
Director of Cardiovascular and Genetic Epidemiology
Intermountain Heart Institute
Intermountain Medical Center
Salt Lake City, Utah 

MedicalResearch.com: What is the background for this study?

Response: Evidence suggests that short-term elevations (even for just a few days) of fine particulate matter air pollution (PM2.5, which is particulate matter less than 2.5 um or about one-thirtieth the diameter of a human hair) is associated with various poor health outcomes among adults, including myocardial infarction, heart failure exacerbation, and worsening of chronic obstructive pulmonary disease symptoms. Studies of long-term exposure to moderately elevated levels of PM2.5 indicate that chronic daily air pollution exposure may contribute to death due to pneumonia and influenza.

Research regarding the association of short-term elevations in PM2.5 has provided some limited evidence of a possible association between short-term PM2.5 increases and infection with respiratory syncytial virus (RSV) or bronchiolitis in children, but scientifically these reports have been weak and unreliable, probably because they have only looked at a period of a few days to a week after short-term PM2.5 elevations. An evaluation of a very large population in a geographic location that provides a wide variation in PM2.5 levels from lowest to highest levels and that examines longer periods of time after the PM2.5 elevations is needed to determine whether a PM2.5 association with lower respiratory infection exists.

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Excessive Rainfall May Be Linked To Autism Through Nitrous Oxide Exposure

MedicalResearch.com Interview with:
Keith Fluegge BS
Institute of Health and Environmental Research (IHER) Cleveland
Graduate School, The Ohio State University, Columbus
Ohio

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The research letter discusses the possible link between rainfall precipitation and risk of autism. Earlier research suggested a link, although there remained quite a bit of skepticism surrounding the findings at the time.

The purpose of the study was to briefly highlight the role of environmental exposure to the agricultural and combustion pollutant, nitrous oxide (N2O), as a possible etiological factor in neurodevelopmental disorders. We have published a series of epidemiological investigations, reviews, and correspondences discussing this possibility. In my continued research on this topic, I learned that rainfall and extreme weather-related events, like hurricanes, drive N2O emissions, especially from nitrogen amended soils. Exposure to this particular air pollutant may, therefore, plausibly undergird the relationship between rainfall precipitation and risk of autism.

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Environmental Pyrethroids May Be Associated With Behavioral Problems in Children

MedicalResearch.com Interview with:
Professor Jean-Francois Viel
Department of Epidemiology and Public Health
University Hospital
Rennes, France

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The use of pyrethroid insecticides has increased substantially throughout the world over the past several decades, replacing organophosphate and carbamate insecticides, because of their chemical potency against many pests, their relatively low mammalian toxicity and their favorable environmental profiles. However, despite the neurotoxicity of these insecticides at high doses, the potential impact of environmental exposure to pyrethroid insecticides on child neurodevelopment has only just started to receive attention.

Using a longitudinal design (PELAGIE mother-child cohort), we were able to assess pyrethroid exposure (trough urine concentrations) both prenatally and during childhood (at 6 years of age). We showed that increased prenatal concentrations of one pyrethroid metabolite (cis-DCCA, a metabolite of permethrin, cypermethrin and cyfluthrin) were associated with internalising difficulties (children showing behaviours that are inhibited and over-controlled).

Moreover, for childhood 3-PBA (a common metabolite of up to 20 synthetic pyrethroid insecticides) concentrations, a positive association was observed with externalising difficulties (children showing behaviours that are under-controlled and having generally a more challenging temperament).

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Unsafe levels of toxic chemicals found in drinking water for six million Americans

MedicalResearch.com Interview with:

Courtney C. Carignan PhD Research Fellow Department of Environmental Health Harvard T.H. Chan School of Public Health

Dr. Courtney Carignan

Courtney C. Carignan PhD
Research Fellow
Department of Environmental Health
Harvard T.H. Chan School of Public Health

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We used mapping technology coupled with drinking water data from EPA to identify military bases, airports, industrial sites, and wastewater treatment plants as major sources of PFOS and PFOA contamination in drinking water. These measurements suggest that at least six million people have drinking water that exceeds the recent EPA health advisorylevels for PFOA and PFOS.

These are chemicals that have been historically manufactured in the US and used widely in consumer products such as stain-proof carpeting, non-stick pans and aqueous firefighting foam. They have been replaced with new generation of shorter-chain fluorinated chemicals, which also do not break down in the environment and may be similarly toxic.

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