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 epidemic of chronic kidney disease of unknown
origin
(CKDu).
Our
central hypothesis is that exposure to high concentrations of airborne contaminants will be associated with kidney
injury, cellular stress, and systemic inflammation in females at-risk for CKDu in Guatemala and Nicaragua.
Nearly all research to date has focused on males, neglecting preliminary data showing that females working in
agriculture and living in agricultural communities in Central American countries are also affected by CKDu.
Additionally, studies to date have largely overlooked consideration of air pollutants as contributors to CKDu
etiology. Given
community
pathways
the potentially high exposures among Central American women from i n-home cooking sources,
ambient air pollution, and agricultural sources, this is an ideal population to explore these potential
linking exposure with kidney injury. In this proposal, we will characterize occupational and non-
occupational airborne exposures to particulate matter (PM), silica, and metals over repeat 8-hour monitoring
periods in 200 female sugarcane workers across three years (Aim 1). We will conduct 8-hour monitoring for each
participant at three time points, twice during the harvest, when exposure is highest, and once during the off-
season. We will evaluate the relationships between individual exposures (PM, silica, and metals) and risk factors
(heat stress and dehydration), mechanisms of injury (kidney injury molecule-1, neutrophil gelatinase-associated
lipocalin, and uromodulin), heat-associated and cellular stress (heat shock protein 70), and inflammation (C-
reactive protein, white blood cells, and cytokines), and kidney biomarkers of effect (serum creatinine and cystatin
C) both acutely (Aim 2) and longitudinally (Aim 3). In addition, we will utilize novel statistical techniques, Bayesian
kernel machine regression (BKMR), weighted quantile sum (WQS) regression and/or quantile g-computation, to
estimate the effects of airborne pollutant mixtures on kidney injury and inflammation (Sub Aim 2.1). The overall
goal of the study is to increase understanding of risk factors for CKDu in females to facilitate future research and
prevention strategies. The proposed research addresses a knowledge gap in understudied, highly exposed
populations: female workers in Guatemala and Nicaragua.
The individual, and combined, contributions of exposures and risk factors on biomarkers of kidney dysfunction,
cellular stress, and inflammation will be examined in this study. This
exposure
conducting
stress,
stress
a) investigate an unexplored
pathway to identify inhalation exposures that may place female agricultural workers at risk by
a robust personal exposure assessment; b) evaluate the relationship between exposure(s), cellular
inflammation, and kidney injury; and c) examine underlying mechanisms by which dehydration and heat
contribute to increased risk of kidney injury. Results will lead to
research will:
intervention trials that will help prevent
CKDu by targeting approaches for vulnerable populations that can be disseminated in the US and internationally.
