PROJECT SUMMARY/ABSTRACT
MesoAmerican Nephropathy (MeN) is a leading cause of death in Central America, resulting in more than
20,000 deaths in the last 20 years. Despite a decade of research on risk factors, including heat and
subsequent dehydration, infectious diseases, chemical exposures, medications and diet, the causes of this
devastating disease remain unclear. The majority of affected individuals are young men working in agricultural
industries, notably sugarcane. Unlike chronic kidney disease (CKD) in other parts of the world, MeN is
characterized by early onset, with patients diagnosed in the 20s or younger. Our Boston University research
team, which has led MeN research in Central America since 2009, has identified evidence of kidney injury and
renal function decline among youth in the region, including elevated prevalence of low eGFR and evidence of
hyperfiltration and urinary biomarkers of kidney injury, both of which may indicate early kidney disease. Our
preliminary data leads us to hypothesize that early life, nephrotoxic exposures contribute to kidney injury and
renal function decline, and that these exposures increase susceptibility to MeN following occupational
exposures later in life. In 2016 (baseline), our team recruited and enrolled over 800 youth in Nicaragua, ages
7-18 years, to set the foundation for a longitudinal cohort of children, adolescents and young adults (the
“NIÑOS” cohort). In this R01, we propose to initiate follow up with these youth, who will be 12-28 years of age
at the start of the study, for a 36-month period. The goals of this study are to: 1) characterize renal function
during youth and young adulthood (annualized change in eGFR) in Nicaragua, a region of high-risk for MeN; 2)
use high-throughput proteomic analysis, including >180 proteins, to develop a predictive biomarker of elevated
annualized decline in eGFR over time; 3) establish the association between a broad spectrum of chemicals
and heavy metals with annualized change in eGFR, using standard and “mixtures” analytic techniques; 4)
conduct a multichemical exposome analysis, including >1500 chemicals, using silicone wristbands to broadly
evaluate the association between personal chemical exposure and renal function; and 4) assess the
association between exposure to heat and renal function in youth using personal heat exposure monitoring.
This project would provide the most comprehensive account to date of renal function and environmental
exposures among a population at high risk of MeN before disease onset, providing critically important etiologic
inferences. Chronic kidney disease of unknown origin is a global public health crisis, with concurrent epidemics
in Sri Lanka, Egypt, and India, as well as throughout Central America. This study will inform international
efforts to understand this phenomenon and reduce incidence.