Particulate exposure and kidney health

Project Summary/Abstract
The overarching goals of this proposal are to contribute to the understanding of the causes, mechanisms, and
potential strategies for prevention of the international epidemic of chronickidney disease of unknown origin
(CKDu). Our central hypothesis is that exposure to high concentrations of air contaminants will be associated
with acute kidney injury in agricultural workers and that heat stress and dehydration will produce adverse
effects on kidney biomarkers. We further hypothesize that this damage occurs through a vasopressin-mediated
injury pathway.
Access to a population of sugarcane workers in cooperation with a major Guatemalan agribusiness will allow
for a study that characterizes sugarcane worker exposure to particulate matter (PM) and it constituents (silica,
glyphosate, and metals) in conjunction with personal factors, including dehydration and heat stress. We will
examine the individual contribution of air contaminant exposure, as well as the combined contribution of
exposure and personal risk factors, on kidney dysfunction. In addition, we will investigate the mechanistic role
of the vasopressin pathway to pathogenesis of CKDu. This
exposure pathway
development
relationship
dehydration
investigate an unexplored
identify may workers at risk for the
of kidney dysfunction by conducting a robust personal exposure assessment, b) evaluate the
between exposure(s) and acute kidney injury, and c) examine underlying mechanisms by which
and heat stress contribute to increased risk of CKDu in conjunction with nephrotoxicant exposures.
research will:
a)
to inhalation exposures that place agricultural
To
metals,
on
evaluate
identify
address this hypothesis, three aims are proposed: Aim 1 focuses on characterizing exposure to PM, silica,
and glyphosate in Guatemalan sugarcane workers and examining the impact of meteorological factors
personal exposure. We will use prospective, quantitative personal measurements in workers. Aim 2 will
the relationship between occupational air contaminant exposure and kidney biomarkers of effect to
workers withincreased risk of cross-shift worsening renal function and inflammation. Aim 3 will
evaluate the potential mechanism by which environmental and individual risk factors induce kidney injury. The
proposed panel study will collect repeat respirable PM personal air samples across two 6-month harvest
seasons in two groups of 60
clinical
Guatemala.
data and
Next,
biological
workers, totaling 120 workers
samples from participants at
. First,
the
we will collect baseline questionnaire and
time of hire at a sugarcane plantation in
we will collect personal air measurements for each participant during the entire work shift to
estimate daily airborne exposure glyphosate, and heavy metals, as well as urine and blood
biomarkers pre- and post-shift t three time points for each worker during the two seasons.
to
silica,
a
Resultsof this research will lead tolarge-scale intervention trials that will help to prevent CKDu by targeting
potential therapeutic approaches for vulnerable populations that can be disseminated internationally.

Grant Number: 3R01ES031585-05S1
NIH Institute/Center: NIH
Principal Investigator: JOHN ADGATE