November 23, 2022 • 24 mins
Agricultural workers provide the food we eat but often face a unique combination of occupational health concerns including increasing incidence of unexplained chronic kidney disease, or chronic kidney disease of unknown etiology (CKDu).
With evidence from a recent Ag Health Study (AHS) in the U.S. directly linking kidney disease to pesticide exposure along with further concern that heat stress may exacerbate the effects of pesticide exposure on kidneys, the study of chronic kidney disease in farmworkers is emerging as a high priority. In this episode, hear from Dr. Chris Vulpe, professor and molecular toxicologist in the Center for Environmental and Human Toxicology at the University of Florida. Dr. Vulpe discusses the interaction between heat stress and pesticide exposure which can lead to kidney damage, and just why this disease has been considered a ‘medical mystery.’
Resources:
SCCAHS Research Project Webpage
Dr. Chris Vulpe Lab Website
Transcripts available here: https://piecenter.com/media/podcast/#transcript
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Episode Transcript
Available transcripts are automatically generated. Complete accuracy is not guaranteed.
Ricky Telg (00:04):
This is Science by the Slice, a podcast from the
University of Florida'sInstitute of Food and
Agricultural Sciences Center forPublic Issues Education. In this
podcast, experts discuss thescience of issues affecting our
daily lives, reveal themotivations behind the decisions
people make, and ultimatelyprovide insight to solutions for
our lives.
Phillip Stokes (00:30):
Welcome to Science by the Slice, I'm
Phillip Stokes. And thisepisode's topic is pretty heavy.
It involves human health anddisease, but also the prospect
of new knowledge and impendinghope to improve health outcomes.
Here's the backstory. Sinceabout the 1990s, there has been
(00:51):
a recognized epidemic that hasbeen the cause of death for tens
of thousands of people indifferent locations all over the
world, including communities inCentral America, Sri Lanka, and
India to name a few. Thisdisease cannot be cured. And
furthermore, scientists havestruggled to determine the exact
causes. It's called chronickidney disease of unknown
(01:14):
etiology, or CKDu. It's aversion of kidney disease
without known etiologies, orcauses. What we know is that
agricultural communities aremost at risk. But it's not like
all agricultural workers areimpacted by this. The most
notable explanations for CKDuare heat stress and dehydration,
(01:35):
and toxic agents such aspesticides, or heavy metals, or
a synergistic effect of both ofthose together. This lingering
scientific uncertainty issomewhat of a roadblock with
respect to prevention, as wellas policy implications. Without
a clear scientific consensus,governments and other
organizations are unsure of howto best coordinate a response to
(01:59):
the problem. So in this episode,I speak with a researcher who's
working toward uncovering themechanisms and molecular
pathways that lead to kidneydamage. And CKDu. Dr. Chris
Vulpe is a professor andmolecular toxicologist in the
Center for Environmental andHuman Toxicology at the
University of Florida. And thisresearch project, led by Dr.
(02:21):
Vulpe is through theSoutheastern Coastal Center for
Agricultural Health and Safety.
So now, let's go to myconversation with Chris, as I
asked him to explain chronickidney disease of unknown
etiology.
Well, Dr. Chris Vulpe, thank youso much for being a guest on
Science by the Slice, to talkabout your research and the
(02:45):
research project you do in theSoutheastern Coastal Center for
Agricultural Health and Safety.
And it has to do with toxicologyand chronic kidney disease of
unknown etiology. EverythingI've ever read about that that
unknown etiology part, there'salways this a very puzzling
component. So what does thatmean? What is chronic kidney
(03:05):
disease of unknown etiology?
Chris Vulpe (03:08):
Well, chronic kidney disease of unknown
etiology, or are called CKDu.
It's a disease that's common inagricultural workers in semi
tropical and tropicalenvironments, which, as the name
sort of implies, we don't knowthe cause of and it's unusual in
(03:29):
that it affects young men andwomen quite early in in life,
and it does not appear to beassociated with some of the
causes of kidney disease thatwe're familiar with such as
diabetes.
Phillip Stokes (03:50):
Just a backup, maybe a moment, the kidneys
serve a pretty essentialfunction in our body, right. So
it is to sort of filter out thewaste and the things that we
bring into it, right?
Chris Vulpe (04:02):
Absolutely. Yeah.
It plays an absolutely essentialrole, and also getting rid of
the toxins that accumulate inyour body, both toxins that
you're exposed to, but we alsogenerate our own toxins the
kidney needs to eliminate.
Phillip Stokes (04:20):
Okay, let's pause and talk a little more
about the kidneys. First off,the kidneys are two bean-shaped
organs about the size of a fist,located inside the abdomen, just
below the ribcage on each sideof the spine. They are a part of
the urinary tract, which is thebody's drainage system for
removing wastes and extra fluidthrough urine. Put very simply,
(04:43):
blood flows into your kidneysthrough an artery. Your kidneys
act as a filter and remove thewaste and toxic substances.
Those wastes are then excretedthrough urine, while the
majority of the fluid flows outof the kidneys through a vein
back into the bloodstreamcontaining The minerals and
nutrients your body needs.
Healthy kidneys filter about ahalf a cup of blood every
(05:04):
minute, maintaining a healthybalance of water, salts and
minerals in your blood. Theyalso secrete a number of
essential hormones that helpcontrol blood pressure, make red
blood cells, and keep your boneshealthy. Yeah, they're extremely
important. And with kidneydisease, this filtration process
is impaired and there can be abuildup of fluid or body waste.
(05:27):
Typical risk factors for kidneydisease include diabetes, high
blood pressure, or heart diseasebut that's not what we're
referring to with CKDu. So let'sjoin back in on my conversation
with Dr. Vulpe as I asked himjust why, in fact, we don't know
more about CKDu given thekidneys essential role in our
(05:48):
bodies.
And being such a vital,important organ, you would think
I think there's this feelingthat we would know almost
everything there is about thisprocess. And so having this new
emerging issue, what is some ofthe data suggesting at this
(06:11):
time? What do we know?
Chris Vulpe (06:12):
Well, I think that's one of the issues with
renal disease is that it can goon for quite a while undetected,
and you can have decreasingrenal function. But until you go
into acute renal failure, itwon't be noticed. I think that
could be one factor that plays arole with why it was under
(06:35):
appreciated for quite a longtime. One of the things that you
asked was, why don't you see it?
CKDu has been noted for quitesome time in in Central America
and India and Bangladesh.
Unfortunately, we still don'thave a good handle on what is
(06:59):
what is causing it. And that isthe kind of the basis of our
work is to try to understandwhat are potential causes as
well as to try to assess to acertain degree how to develop
ways to detect it.
Phillip Stokes (07:15):
So what would you say are some of the risk
factors within the agriculturalindustry and within laborers?
What are some of those commondenominators and risk factors
associated with CKDu?
Chris Vulpe (07:26):
Well, for sure, it's being in a hot and humid
climate and those appears to beimportant. You know, however,
there are places where theredoesn't appear to be a high
prevalence of CKDu, such asCuba, and other places which
have very similar climates. Soit's been a little bit
(07:47):
mysterious, why it would appearin some places and, and not
others with very seriousclimate. And the thought is,
there must be something else incombination with the heat, the
humidity, and then theassociated dehydration that can
sometimes occur in people insuch an environment. And
(08:10):
together, you know, thesefactors or risk factors increase
the likelihood of developingCKDu.
Phillip Stokes (08:19):
So as a researcher, as a toxicologist,
what are the key questions youand your colleagues are asking
to learn more about thisdisease?
Chris Vulpe (08:28):
Well, one of the key factors that has been
considered not just by us, butby many people is the potential
role that chemicals andagricultural chemicals in
particular, could play a role inthe development of CKDu. And
several chemicals have beenidentified as potentially
(08:51):
contributing, but there's noreal, I guess, smoking gun, to
absolutely demonstrate thatthey're involved.
Phillip Stokes (09:00):
So what is your research aiming to do? Could you
just set the stage for whatyou're doing here at the
University of Florida?
Chris Vulpe (09:07):
So there are a lot of possible factors which could
be contributing to chronickidney disease in agricultural
workers. In addition to thechemical exposures. There's also
been speculation about otherfactors such as airborne
pollution and other things, butit's very difficult in a study
(09:29):
of people to make a causalconnection between exposure and
the development of disease. Sowhat we're doing is trying to
test the hypothesis that it'sthe combination of heat and
exposure to agriculturalchemicals. And we're looking
(09:52):
specifically at three chemicalsright now. Glyphosate, which is
the active ingredient inRoundup, Permethrin and
Paraquat. And in animal studies,which are more controlled than
human studies in which you cancontrol the exposure, we're
(10:12):
trying to determine whether thecombination of heat and
pesticide exposure leads to thedevelopment of kidney disease.
Phillip Stokes (10:22):
So if you could just share with us how are you
doing this? What is yourmethodical approach here,
because I know that your studyis a bit novel and a bit unique
and different than some of theprevious studies. I know you're
using laboratory animals. So ifyou could just kind of paint a
picture and tell us a littlemore about that.
Chris Vulpe (10:38):
Most of the previous studies of CKDu have
been epidemiologic studiesfocused on human populations,
but in those sorts of studies,it can be difficult to determine
what are the cause of disease.
So we're doing a controlledstudy using an animal model,
(10:58):
specifically rats to determinewhether the combination of heat
exposure and chemical exposuretogether can lead to kidney
disease. And if these studiesfind a relationship between the
two, then that provides somesupport for the idea that in
(11:20):
people it's similar exposuresthat could be contributing to
the disease. However, of course,it could turn out that we're
wrong and then in fact, thesechemicals play no role. So we're
trying to test that hypothesisthat these chemicals are playing
a role. The other thing I'd sayit's it's different in
(11:41):
epidemiologic studies in people,people are exposed to a whole
bunch of things at the sametime. So as a result, it's very
difficult to tease out which isthe key exposure, is it the heat
alone? Is it the heat plus thischemical, the heat plus that
chemical? Or it's possible, ofcourse, that it could be, you
(12:04):
know, the combination of heatand one or more other risk
factors or chemical exposures.
And so the animal model allowsus to sort of systematically
test what are the possiblecauses of the disease. And of
course, once you identify apossible cause, and that allows
(12:25):
you to focus your studies andpeople to try to, you know,
better understand it. If we havegood evidence that, you know,
let's say one chemical plays animportant role, then we can do
more focused studies on that inin human studies, and really try
to see if there is arelationship.
Phillip Stokes (12:44):
Right. I mean, that's such an interesting
point, there are so manyfactors, humans are exposed to
so many different, you know,things in our environment, and
the things we eat are ourlifestyle, our genetics, and
you're able to pinpoint,isolate, like you said, in a
controlled experiment using alive animal species that has a
(13:04):
working system, right? And soyou can't replicate that
anywhere else, right?
Chris Vulpe (13:10):
Well, yeah, I mean, animal models are, in some ways,
a model of last resort. I mean,if you can do the study in
anything else, you want to dothat, because you know, that's
the the most appropriate and themost moral way to do the work.
Unfortunately, at present, wedon't have very good cell based
(13:35):
models for understanding theeffects of chemicals on the
kidney. Now, I'm not saying thatthere aren't approaches that are
being developed and there's beentremendous work with the
development of things such asIPSC-based kidney cells, but
unfortunately, at the currenttime, there really isn't an
(13:56):
adequate physiologic model to beable to study this in cell
culture based method, which isthe why that we unfortunately
have to use animal models. Ofcourse, you know, always the
goal with animal models is thatit's being used to inform the
human studies, and you do themin such a way as to minimize the
(14:18):
number of animals to theabsolute minimum of the number
number that you need to use inorder to get the results that
you you need.
Phillip Stokes (14:28):
Well, I really appreciate you saying that. And
I think that's really importantfor, you know, our listeners to
hear who may be unfamiliar withlaboratory animal studies. And
so that's some good backgroundknowledge behind that. What are
some of the baseline findings orthe baseline data that you have
right now? And then yeah, maybewe can talk about some of the
(14:49):
further implications with humanstudies.
Chris Vulpe (14:52):
Yeah, well, I mean, in order to understand what the
combined effects are of heat andpesticide exposure, you really
have to understand In theindividual exposures. So a lot
of the work that we've beenfocused on for the last period
of time, has been understandingthe individual effects of
pesticide exposure alone andheat exposure alone and the
(15:15):
first acute effects on thekidney, as well as the chronic
effects. Because, you know, asyou can surmise, you know,
farmworkers are not just exposedonce to heat and pesticide
exposure, it is occurring on aregular basis, and they have
(15:38):
repeated exposures. So we'vebeen focusing on trying to
understand what the individualeffects of repeated exposures is
on the kidney in the animalmodel. And our initial findings
have indicated that these areboth heat and different chemical
exposures are significantstressors on the kidney. So
(16:02):
we've been trying to understandwhat the stress is, and what
parts of the kidney areaffected. And today, we have
seen some evidence of effect onthe filtration part of the
kidney, which is called theglomerulus.
Phillip Stokes (16:21):
Are you finding these stresses are more adverse
in in conjunction with oneanother with the heat and the
chemical exposure? Is one morenoteworthy than the other? Or is
it? Is it this combination?
Chris Vulpe (16:36):
Yeah, I mean, actually, to date, that's where
we're going right now is tostudy that combination. So we've
been focused on the individual.
And then the focus of thisstudy, is really now to ask that
question, what is thecombination going to do? And
what happens with a combinationrepeated over time, for a long
period of time? And what doesthis repeated stress on the
(17:00):
kidney do? And does that resultin a kidney disease that looks
similar to what's seen inpeople? And one of the ways that
you determine that is by lookingat the kidney by doing what's
called pathology, as well aslooking at what are the
molecular events that areoccurring in the kidney? You
(17:23):
know, what changes arehappening? And seeing are they
similar to what we see inpeople?
Phillip Stokes (17:31):
That's fascinating that you're able to,
like you said, isolate certaincells within the kidney, and
you're able to look at it onsuch a smaller scale than you
would add an epidemiologicalstudy, like you mentioned
previously. So you have thatbaseline data. And of course, I
know that you have more researchto carry out. But what are some
(17:54):
of the implications and some ofthe next steps within the
research process?
Chris Vulpe (17:58):
What we're involved in is, is trying to ask, How
similar are the changes thatwe're seeing in the rat to
changes that are observed inpeople? Now you're right, we
can't measure what's going on inthe kidney in people. But what
you can do is you can use whatare called biomarkers. So
(18:20):
biomarkers is really just afancy term for basically a lab
test. And we use biomarkers allthe time in, you know, for
instance, when you get a heartattack, right, they measure the
heart proteins, or you look atliver disease, you look at some
of the liver proteins, and youcan do the exact same thing for
kidney. And these biomarkers cantell you, you know, are the is
(18:45):
the kidney being injured. Butnot only that, they can tell you
where in the kidney, what what'sbeing injured. One of the things
that we're working on now is tolook at populations where they
have chronic kidney disease ofunknown etiology, and look at
the biomarkers in their urine.
And first of all, see, well,what are the biomarkers? Is
(19:07):
there evidence of kidneydisease? And then secondly, are
the changes that we see inpeople look like the changes
that we see in our animal model?
And again, this is another wayto ask the question is the
disease that we're seeing in ananimal model, similar to what
we're seeing in people, or moreimportantly, is what is being
(19:31):
seen in people reflected in thework that we're doing in an
animal model? And so they kindof build on each other, right?
You can't do these sorts ofstudies in people where you do
exposures and heat, but we canask, what's the effect on the
biomarkers that we can take thebiomarkers from people and say,
hey, well, does this look likewhat we're seeing in the animal
(19:54):
model? And if they are, then wecan sort of infer that maybe the
mechanisms are similar. Theykind of add value to each other.
And you can get the mechanisticinformation from the animal
model, which can help inform thehuman studies. Because I think
the other sort of goal of this,of developing these biomarkers
(20:17):
is the idea of trying to developearly indicators, right, so that
you can detect a disease beforethey get fulminant kidney
failure, you know, so that's theother kind of goal with
biomarkers is to be earlydisease indicators. And if you
can measure it in urine, thenyou know, it's very simple,
(20:39):
easy, fast, and can help predictthe people who are going to be
at risk, because they've alreadygot some evidence of kidney
disease. And that could bereally helpful in preventing
them from going on to developrenal failure, because there is
no treatment for renal failureexcept dialysis or transplant.
And so if we can preventfarmworkers from developing
(21:03):
renal failure, then that will bea great, you know, outcome.
Phillip Stokes (21:08):
No, I think that's great. Dr. Vulpe, is
there anything else we didn'ttouch on that you'd like to say,
before we close out the podcast?
Chris Vulpe (21:14):
You know, we know very little about CKDu, even in
places where it's pretty wellstudied. But here in the U.S. I
would say it's even worse,because the healthcare system is
such that we don't have a wholelot of information about how
prevalent it is here in Florida,and many farmworkers, if they
(21:34):
develop kidney disease, thenthey're going to not be able to
continue their work. And thoseindividuals may not even be
identified as having thedisease. So I guess what I'm
saying is, I think there's anunseen potential burden of this
disease. And because of thenature of transitory
agricultural work with oftenmigrant populations, that this
(21:59):
disease can be hidden or not benoticed, perhaps if it was
occurring in a, you know, apopulation with better health
care and a more stable medicalcare system.
Phillip Stokes (22:12):
Yeah, I mean, it sounds like in a way, we don't
have a certain amount of data,because some of those data
points come in through ourhealthcare system, right,
through doctors offices, and ERsand hospitals in different
places. But yeah, when you havea group of individuals that
maybe don't have as much access,or who are more marginalized,
(22:33):
potentially, it may be harder toidentify a cause and effect. Is
that basically kind of whatyou're getting at?
Chris Vulpe (22:39):
Yeah, I think that's part of it. I also think
if they have the disease, theymay not continue to work in
agriculture. And so those peoplewill just sort of disappear. And
so you'll you'll look at yourpopulation, and you'll say, Oh,
they're healthy. But that'sbecause the people who weren't
healthy are no longer there. Andso when you have a turnover of
(22:59):
the population, I think that canhide the disease. So I think
that's potentially also gettingat to one of the things that you
were mentioning earlier, whyhaven't we noticed this? And the
question is who's asking, right?
And I think probably if you askthe Farmworker populations in
many of these places, they'dsay, Yeah, this has been with
us. But you know, maybe it's notsomething that people have
(23:20):
noticed.
Phillip Stokes (23:23):
And potentially, it has been explained as the
cause from being one of thosemore traditional causes, like
diabetes or something like that.
Chris Vulpe (23:32):
For sure. For sure, because a medical practitioner,
also, they're not going to belooking for this necessarily.
Phillip Stokes (23:37):
Right.
Chris Vulpe (23:38):
At Least not in places where it's not familiar,
you know, they're gonna think,oh, it's diabetes, or it's
something else?
Phillip Stokes (23:44):
Well, I think that does certainly add to kind
of, like we talked about at thebeginning, the mysterious nature
of this, just the puzzlingnature of this disease, which I
think makes your researchproject and all of those that
are involved, so needed and sopowerful. So I just want to
thank you for talking with metoday Dr. Vulpe on Science by
(24:06):
the Slice. I really appreciateyour time.
Ricky Telg (24:11):
Science by the Slice is produced by the UF/IFAS
Center for Public IssuesEducation in Agriculture and
Natural Resources. Thanks forlistening to today's episode.
Subscribe to Science by theSlice on your favorite podcast
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(24:34):
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We'd love to hear from you. Ifyou enjoyed today's episode,
consider sharing with a friendor colleague. Until next time,
thanks for listening to Scienceby the Slice.
This is Science by the Slice, a podcast from the
University of Florida'sInstitute of Food and
Agricultural Sciences Center forPublic Issues Education. In this
podcast, experts discuss thescience of issues affecting our
daily lives, reveal themotivations behind the decisions
people make, and ultimatelyprovide insight to solutions for
our lives.
Phillip Stokes (00:30):
Welcome to Science by the Slice, I'm
Phillip Stokes. And thisepisode's topic is pretty heavy.
It involves human health anddisease, but also the prospect
of new knowledge and impendinghope to improve health outcomes.
Here's the backstory. Sinceabout the 1990s, there has been
(00:51):
a recognized epidemic that hasbeen the cause of death for tens
of thousands of people indifferent locations all over the
world, including communities inCentral America, Sri Lanka, and
India to name a few. Thisdisease cannot be cured. And
furthermore, scientists havestruggled to determine the exact
causes. It's called chronickidney disease of unknown
(01:14):
etiology, or CKDu. It's aversion of kidney disease
without known etiologies, orcauses. What we know is that
agricultural communities aremost at risk. But it's not like
all agricultural workers areimpacted by this. The most
notable explanations for CKDuare heat stress and dehydration,
(01:35):
and toxic agents such aspesticides, or heavy metals, or
a synergistic effect of both ofthose together. This lingering
scientific uncertainty issomewhat of a roadblock with
respect to prevention, as wellas policy implications. Without
a clear scientific consensus,governments and other
organizations are unsure of howto best coordinate a response to
(01:59):
the problem. So in this episode,I speak with a researcher who's
working toward uncovering themechanisms and molecular
pathways that lead to kidneydamage. And CKDu. Dr. Chris
Vulpe is a professor andmolecular toxicologist in the
Center for Environmental andHuman Toxicology at the
University of Florida. And thisresearch project, led by Dr.
(02:21):
Vulpe is through theSoutheastern Coastal Center for
Agricultural Health and Safety.
So now, let's go to myconversation with Chris, as I
asked him to explain chronickidney disease of unknown
etiology.
Well, Dr. Chris Vulpe, thank youso much for being a guest on
Science by the Slice, to talkabout your research and the
(02:45):
research project you do in theSoutheastern Coastal Center for
Agricultural Health and Safety.
And it has to do with toxicologyand chronic kidney disease of
unknown etiology. EverythingI've ever read about that that
unknown etiology part, there'salways this a very puzzling
component. So what does thatmean? What is chronic kidney
(03:05):
disease of unknown etiology?
Chris Vulpe (03:08):
Well, chronic kidney disease of unknown
etiology, or are called CKDu.
It's a disease that's common inagricultural workers in semi
tropical and tropicalenvironments, which, as the name
sort of implies, we don't knowthe cause of and it's unusual in
(03:29):
that it affects young men andwomen quite early in in life,
and it does not appear to beassociated with some of the
causes of kidney disease thatwe're familiar with such as
diabetes.
Phillip Stokes (03:50):
Just a backup, maybe a moment, the kidneys
serve a pretty essentialfunction in our body, right. So
it is to sort of filter out thewaste and the things that we
bring into it, right?
Chris Vulpe (04:02):
Absolutely. Yeah.
It plays an absolutely essentialrole, and also getting rid of
the toxins that accumulate inyour body, both toxins that
you're exposed to, but we alsogenerate our own toxins the
kidney needs to eliminate.
Phillip Stokes (04:20):
Okay, let's pause and talk a little more
about the kidneys. First off,the kidneys are two bean-shaped
organs about the size of a fist,located inside the abdomen, just
below the ribcage on each sideof the spine. They are a part of
the urinary tract, which is thebody's drainage system for
removing wastes and extra fluidthrough urine. Put very simply,
(04:43):
blood flows into your kidneysthrough an artery. Your kidneys
act as a filter and remove thewaste and toxic substances.
Those wastes are then excretedthrough urine, while the
majority of the fluid flows outof the kidneys through a vein
back into the bloodstreamcontaining The minerals and
nutrients your body needs.
Healthy kidneys filter about ahalf a cup of blood every
(05:04):
minute, maintaining a healthybalance of water, salts and
minerals in your blood. Theyalso secrete a number of
essential hormones that helpcontrol blood pressure, make red
blood cells, and keep your boneshealthy. Yeah, they're extremely
important. And with kidneydisease, this filtration process
is impaired and there can be abuildup of fluid or body waste.
(05:27):
Typical risk factors for kidneydisease include diabetes, high
blood pressure, or heart diseasebut that's not what we're
referring to with CKDu. So let'sjoin back in on my conversation
with Dr. Vulpe as I asked himjust why, in fact, we don't know
more about CKDu given thekidneys essential role in our
(05:48):
bodies.
And being such a vital,important organ, you would think
I think there's this feelingthat we would know almost
everything there is about thisprocess. And so having this new
emerging issue, what is some ofthe data suggesting at this
(06:11):
time? What do we know?
Chris Vulpe (06:12):
Well, I think that's one of the issues with
renal disease is that it can goon for quite a while undetected,
and you can have decreasingrenal function. But until you go
into acute renal failure, itwon't be noticed. I think that
could be one factor that plays arole with why it was under
(06:35):
appreciated for quite a longtime. One of the things that you
asked was, why don't you see it?
CKDu has been noted for quitesome time in in Central America
and India and Bangladesh.
Unfortunately, we still don'thave a good handle on what is
(06:59):
what is causing it. And that isthe kind of the basis of our
work is to try to understandwhat are potential causes as
well as to try to assess to acertain degree how to develop
ways to detect it.
Phillip Stokes (07:15):
So what would you say are some of the risk
factors within the agriculturalindustry and within laborers?
What are some of those commondenominators and risk factors
associated with CKDu?
Chris Vulpe (07:26):
Well, for sure, it's being in a hot and humid
climate and those appears to beimportant. You know, however,
there are places where theredoesn't appear to be a high
prevalence of CKDu, such asCuba, and other places which
have very similar climates. Soit's been a little bit
(07:47):
mysterious, why it would appearin some places and, and not
others with very seriousclimate. And the thought is,
there must be something else incombination with the heat, the
humidity, and then theassociated dehydration that can
sometimes occur in people insuch an environment. And
(08:10):
together, you know, thesefactors or risk factors increase
the likelihood of developingCKDu.
Phillip Stokes (08:19):
So as a researcher, as a toxicologist,
what are the key questions youand your colleagues are asking
to learn more about thisdisease?
Chris Vulpe (08:28):
Well, one of the key factors that has been
considered not just by us, butby many people is the potential
role that chemicals andagricultural chemicals in
particular, could play a role inthe development of CKDu. And
several chemicals have beenidentified as potentially
(08:51):
contributing, but there's noreal, I guess, smoking gun, to
absolutely demonstrate thatthey're involved.
Phillip Stokes (09:00):
So what is your research aiming to do? Could you
just set the stage for whatyou're doing here at the
University of Florida?
Chris Vulpe (09:07):
So there are a lot of possible factors which could
be contributing to chronickidney disease in agricultural
workers. In addition to thechemical exposures. There's also
been speculation about otherfactors such as airborne
pollution and other things, butit's very difficult in a study
(09:29):
of people to make a causalconnection between exposure and
the development of disease. Sowhat we're doing is trying to
test the hypothesis that it'sthe combination of heat and
exposure to agriculturalchemicals. And we're looking
(09:52):
specifically at three chemicalsright now. Glyphosate, which is
the active ingredient inRoundup, Permethrin and
Paraquat. And in animal studies,which are more controlled than
human studies in which you cancontrol the exposure, we're
(10:12):
trying to determine whether thecombination of heat and
pesticide exposure leads to thedevelopment of kidney disease.
Phillip Stokes (10:22):
So if you could just share with us how are you
doing this? What is yourmethodical approach here,
because I know that your studyis a bit novel and a bit unique
and different than some of theprevious studies. I know you're
using laboratory animals. So ifyou could just kind of paint a
picture and tell us a littlemore about that.
Chris Vulpe (10:38):
Most of the previous studies of CKDu have
been epidemiologic studiesfocused on human populations,
but in those sorts of studies,it can be difficult to determine
what are the cause of disease.
So we're doing a controlledstudy using an animal model,
(10:58):
specifically rats to determinewhether the combination of heat
exposure and chemical exposuretogether can lead to kidney
disease. And if these studiesfind a relationship between the
two, then that provides somesupport for the idea that in
(11:20):
people it's similar exposuresthat could be contributing to
the disease. However, of course,it could turn out that we're
wrong and then in fact, thesechemicals play no role. So we're
trying to test that hypothesisthat these chemicals are playing
a role. The other thing I'd sayit's it's different in
(11:41):
epidemiologic studies in people,people are exposed to a whole
bunch of things at the sametime. So as a result, it's very
difficult to tease out which isthe key exposure, is it the heat
alone? Is it the heat plus thischemical, the heat plus that
chemical? Or it's possible, ofcourse, that it could be, you
(12:04):
know, the combination of heatand one or more other risk
factors or chemical exposures.
And so the animal model allowsus to sort of systematically
test what are the possiblecauses of the disease. And of
course, once you identify apossible cause, and that allows
(12:25):
you to focus your studies andpeople to try to, you know,
better understand it. If we havegood evidence that, you know,
let's say one chemical plays animportant role, then we can do
more focused studies on that inin human studies, and really try
to see if there is arelationship.
Phillip Stokes (12:44):
Right. I mean, that's such an interesting
point, there are so manyfactors, humans are exposed to
so many different, you know,things in our environment, and
the things we eat are ourlifestyle, our genetics, and
you're able to pinpoint,isolate, like you said, in a
controlled experiment using alive animal species that has a
(13:04):
working system, right? And soyou can't replicate that
anywhere else, right?
Chris Vulpe (13:10):
Well, yeah, I mean, animal models are, in some ways,
a model of last resort. I mean,if you can do the study in
anything else, you want to dothat, because you know, that's
the the most appropriate and themost moral way to do the work.
Unfortunately, at present, wedon't have very good cell based
(13:35):
models for understanding theeffects of chemicals on the
kidney. Now, I'm not saying thatthere aren't approaches that are
being developed and there's beentremendous work with the
development of things such asIPSC-based kidney cells, but
unfortunately, at the currenttime, there really isn't an
(13:56):
adequate physiologic model to beable to study this in cell
culture based method, which isthe why that we unfortunately
have to use animal models. Ofcourse, you know, always the
goal with animal models is thatit's being used to inform the
human studies, and you do themin such a way as to minimize the
(14:18):
number of animals to theabsolute minimum of the number
number that you need to use inorder to get the results that
you you need.
Phillip Stokes (14:28):
Well, I really appreciate you saying that. And
I think that's really importantfor, you know, our listeners to
hear who may be unfamiliar withlaboratory animal studies. And
so that's some good backgroundknowledge behind that. What are
some of the baseline findings orthe baseline data that you have
right now? And then yeah, maybewe can talk about some of the
(14:49):
further implications with humanstudies.
Chris Vulpe (14:52):
Yeah, well, I mean, in order to understand what the
combined effects are of heat andpesticide exposure, you really
have to understand In theindividual exposures. So a lot
of the work that we've beenfocused on for the last period
of time, has been understandingthe individual effects of
pesticide exposure alone andheat exposure alone and the
(15:15):
first acute effects on thekidney, as well as the chronic
effects. Because, you know, asyou can surmise, you know,
farmworkers are not just exposedonce to heat and pesticide
exposure, it is occurring on aregular basis, and they have
(15:38):
repeated exposures. So we'vebeen focusing on trying to
understand what the individualeffects of repeated exposures is
on the kidney in the animalmodel. And our initial findings
have indicated that these areboth heat and different chemical
exposures are significantstressors on the kidney. So
(16:02):
we've been trying to understandwhat the stress is, and what
parts of the kidney areaffected. And today, we have
seen some evidence of effect onthe filtration part of the
kidney, which is called theglomerulus.
Phillip Stokes (16:21):
Are you finding these stresses are more adverse
in in conjunction with oneanother with the heat and the
chemical exposure? Is one morenoteworthy than the other? Or is
it? Is it this combination?
Chris Vulpe (16:36):
Yeah, I mean, actually, to date, that's where
we're going right now is tostudy that combination. So we've
been focused on the individual.
And then the focus of thisstudy, is really now to ask that
question, what is thecombination going to do? And
what happens with a combinationrepeated over time, for a long
period of time? And what doesthis repeated stress on the
(17:00):
kidney do? And does that resultin a kidney disease that looks
similar to what's seen inpeople? And one of the ways that
you determine that is by lookingat the kidney by doing what's
called pathology, as well aslooking at what are the
molecular events that areoccurring in the kidney? You
(17:23):
know, what changes arehappening? And seeing are they
similar to what we see inpeople?
Phillip Stokes (17:31):
That's fascinating that you're able to,
like you said, isolate certaincells within the kidney, and
you're able to look at it onsuch a smaller scale than you
would add an epidemiologicalstudy, like you mentioned
previously. So you have thatbaseline data. And of course, I
know that you have more researchto carry out. But what are some
(17:54):
of the implications and some ofthe next steps within the
research process?
Chris Vulpe (17:58):
What we're involved in is, is trying to ask, How
similar are the changes thatwe're seeing in the rat to
changes that are observed inpeople? Now you're right, we
can't measure what's going on inthe kidney in people. But what
you can do is you can use whatare called biomarkers. So
(18:20):
biomarkers is really just afancy term for basically a lab
test. And we use biomarkers allthe time in, you know, for
instance, when you get a heartattack, right, they measure the
heart proteins, or you look atliver disease, you look at some
of the liver proteins, and youcan do the exact same thing for
kidney. And these biomarkers cantell you, you know, are the is
(18:45):
the kidney being injured. Butnot only that, they can tell you
where in the kidney, what what'sbeing injured. One of the things
that we're working on now is tolook at populations where they
have chronic kidney disease ofunknown etiology, and look at
the biomarkers in their urine.
And first of all, see, well,what are the biomarkers? Is
(19:07):
there evidence of kidneydisease? And then secondly, are
the changes that we see inpeople look like the changes
that we see in our animal model?
And again, this is another wayto ask the question is the
disease that we're seeing in ananimal model, similar to what
we're seeing in people, or moreimportantly, is what is being
(19:31):
seen in people reflected in thework that we're doing in an
animal model? And so they kindof build on each other, right?
You can't do these sorts ofstudies in people where you do
exposures and heat, but we canask, what's the effect on the
biomarkers that we can take thebiomarkers from people and say,
hey, well, does this look likewhat we're seeing in the animal
(19:54):
model? And if they are, then wecan sort of infer that maybe the
mechanisms are similar. Theykind of add value to each other.
And you can get the mechanisticinformation from the animal
model, which can help inform thehuman studies. Because I think
the other sort of goal of this,of developing these biomarkers
(20:17):
is the idea of trying to developearly indicators, right, so that
you can detect a disease beforethey get fulminant kidney
failure, you know, so that's theother kind of goal with
biomarkers is to be earlydisease indicators. And if you
can measure it in urine, thenyou know, it's very simple,
(20:39):
easy, fast, and can help predictthe people who are going to be
at risk, because they've alreadygot some evidence of kidney
disease. And that could bereally helpful in preventing
them from going on to developrenal failure, because there is
no treatment for renal failureexcept dialysis or transplant.
And so if we can preventfarmworkers from developing
(21:03):
renal failure, then that will bea great, you know, outcome.
Phillip Stokes (21:08):
No, I think that's great. Dr. Vulpe, is
there anything else we didn'ttouch on that you'd like to say,
before we close out the podcast?
Chris Vulpe (21:14):
You know, we know very little about CKDu, even in
places where it's pretty wellstudied. But here in the U.S. I
would say it's even worse,because the healthcare system is
such that we don't have a wholelot of information about how
prevalent it is here in Florida,and many farmworkers, if they
(21:34):
develop kidney disease, thenthey're going to not be able to
continue their work. And thoseindividuals may not even be
identified as having thedisease. So I guess what I'm
saying is, I think there's anunseen potential burden of this
disease. And because of thenature of transitory
agricultural work with oftenmigrant populations, that this
(21:59):
disease can be hidden or not benoticed, perhaps if it was
occurring in a, you know, apopulation with better health
care and a more stable medicalcare system.
Phillip Stokes (22:12):
Yeah, I mean, it sounds like in a way, we don't
have a certain amount of data,because some of those data
points come in through ourhealthcare system, right,
through doctors offices, and ERsand hospitals in different
places. But yeah, when you havea group of individuals that
maybe don't have as much access,or who are more marginalized,
(22:33):
potentially, it may be harder toidentify a cause and effect. Is
that basically kind of whatyou're getting at?
Chris Vulpe (22:39):
Yeah, I think that's part of it. I also think
if they have the disease, theymay not continue to work in
agriculture. And so those peoplewill just sort of disappear. And
so you'll you'll look at yourpopulation, and you'll say, Oh,
they're healthy. But that'sbecause the people who weren't
healthy are no longer there. Andso when you have a turnover of
(22:59):
the population, I think that canhide the disease. So I think
that's potentially also gettingat to one of the things that you
were mentioning earlier, whyhaven't we noticed this? And the
question is who's asking, right?
And I think probably if you askthe Farmworker populations in
many of these places, they'dsay, Yeah, this has been with
us. But you know, maybe it's notsomething that people have
(23:20):
noticed.
Phillip Stokes (23:23):
And potentially, it has been explained as the
cause from being one of thosemore traditional causes, like
diabetes or something like that.
Chris Vulpe (23:32):
For sure. For sure, because a medical practitioner,
also, they're not going to belooking for this necessarily.
Phillip Stokes (23:37):
Right.
Chris Vulpe (23:38):
At Least not in places where it's not familiar,
you know, they're gonna think,oh, it's diabetes, or it's
something else?
Phillip Stokes (23:44):
Well, I think that does certainly add to kind
of, like we talked about at thebeginning, the mysterious nature
of this, just the puzzlingnature of this disease, which I
think makes your researchproject and all of those that
are involved, so needed and sopowerful. So I just want to
thank you for talking with metoday Dr. Vulpe on Science by
(24:06):
the Slice. I really appreciateyour time.
Ricky Telg (24:11):
Science by the Slice is produced by the UF/IFAS
Center for Public IssuesEducation in Agriculture and
Natural Resources. Thanks forlistening to today's episode.
Subscribe to Science by theSlice on your favorite podcast
app and give us a rating orreview as well. Have a question
or comment? Send us an email topiecenter@ifas.ufl.edu. That's
(24:34):
piecenter, all one word, atifas, I-F-A-S, dot ufl dot edu.
We'd love to hear from you. Ifyou enjoyed today's episode,
consider sharing with a friendor colleague. Until next time,
thanks for listening to Scienceby the Slice.
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