Faculty from Texas A&M’s School of Public Health teamed up with other institutions across
the state to show how the herbicide paraquat caused a kidney disease epidemic in Central
America.
The mystery of what’s behind a kidney disease epidemic occurring in Central America may
have been solved.
A study published in the Clinical Journal of the American Society of Nephrology links
a common agricultural chemical called paraquat to the rise of kidney disease cases in young
Mesoamericans.
The ongoing epidemic first came to light in the early 2000’s and affects primarily young
men and women in agricultural communities in Pacific coastal regions of Mexico and Central
America, which include some of the world’s poorest communities.
Known now as Mesoamerican nephropathy, it is a kidney disease of unknown etiology, and
patients don’t have the underlying health conditions that usually precede kidney disease,
such as hypertension, diabetes or obesity.
They are also not in later stages of life, being affected in their 20’s and 30’s.
The disease — which is caused by damaged kidneys that are unable to effectively filter
waste products from blood — can be deadly, especially without modern life-saving treatments
that may be available elsewhere in the world.
A team including faculty at the Texas A&M University School of Public Health previously
conducted the foundational research that described the clinical and pathological features of
the disease, which are important early steps during an emerging epidemic, especially one
presenting new clinical features.
For the past eight years, the team has also been looking for the underlying cause of this
disease.
Possible causes of Mesoamerican nephropathy have been thought to include infection, toxic
exposure to heavy metals or agricultural chemicals, or another yet unknown exposure, and may be
compounded by heat stress or dehydration.
This newest study took a closer look at one of these possible causes and found evidence
pointing to it being responsible for Mesoamerican nephropathy as well as a possible way it causes
kidney damage.
Dr. Rebecca Fischer, assistant professor at the School of Public Health, along with colleagues
from Houston Methodist Hospital, Baylor College of Medicine, The University of Texas MD Anderson
Cancer Center and other institutions, investigated the role that paraquat may play in Mesoamerican
nephropathy.
Fischer’s current research is funded by the National Institutes of Health.
Paraquat is an herbicide used in agriculture around the world.
It works by generating reactive oxygen species (ROS) that are known to damage tissues.
Heavy metals like cadmium, mercury and arsenic also generate ROS and have been associated
— along with other ROS-generating agricultural chemicals — with kidney damage.
Exposure to high doses of paraquat have been linked with damage to kidneys and other organs,
but long-term exposure to lower doses such as those seen among agricultural works has
not been studied.
To investigate the potential role of paraquat in Mesoamerican nephropathy, the researchers
surveyed immigrants from Central America who had kidney disease and were patients at an
outpatient dialysis clinic in Houston, Texas.
They examined samples of human kidney tissues from Fischer’s previous study, and compared
kidney tissue samples from animal models injected with low doses of paraquat and a control group
of animal models not exposed to paraquat.
They also analyzed the expression of two genes, OCT2 and MATE1, known to transport paraquat
and heavy metals into and out of kidney cells.
The survey included 52 patients who exhibited signs of Mesoamerican nephropathy and 63 patients
with different types of kidney failure.
The patients in the Mesoamerican nephropathy group were younger, 96 percent male and most
had worked in agriculture prior to immigrating to the United States, making long-term exposure
to paraquat more likely.
Analysis of human and animal model kidney tissue revealed damage consistent with chronic
kidney disease.
The researchers also found increased expression of OCT2 and decreased MATE1 expression in
male animal models injected with paraquat.
Additionally, kidney damage in female animal models was less severe, which is consistent
with a pattern of disease observed in Mesoamerican nephropathy.
These findings point several additional areas of study, including to OCT2 and MATE1 expression
and differences in expression between men and women.
This study sheds light on a possible cause for Mesoamerican nephropathy.
The research also points to ROS generation as a likely mechanism for kidney damage in
these cases as well as the role changes in expression of genes like OCT2 and MATE1 may
play.
This study and additional research can help further clarify the potential dangers of agricultural
chemicals like paraquat and highlight the need to protect agriculture workers against
agrochemicals and other agents they might be exposed to in the environment in the future.