# Role of Genetic Susceptibility in the Central American Kidney Disease Epidemic

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $678,087

## Abstract

PROJECT SUMMARY
Extraordinarily high rates of chronic kidney disease have been observed on the Pacific coast of
several Central American countries including Nicaragua, El Salvador, Honduras, Guatemala,
Costa Rica, and Southern Mexico. This increasingly recognized epidemic of kidney disease,
known as Mesoamerican Nephropathy (MeN), is not associated with traditional risk factors
such as diabetes or hypertension, and affects predominately young men who work in
agriculture. Environmental factors such as heat stress, pesticides, infectious diseases, and
many others have been proposed as potential explanations, but no clear cause has emerged.
The postulated risk factors do not appear to be unique to the affected region, and they do not
explain why some agricultural workers get kidney disease while others do not. We propose
that genetic susceptibility is a major contributor to MeN risk, a hypothesis that we have
strengthened by documenting striking familial clustering of disease. We have built strong
relationships with local physicians, workers' groups, industry, and government in a MeN
hotspot in Nicaragua. We have also built an interdisciplinary team with expertise in nephrology,
genetics, epidemiology, and statistics. We have successfully enrolled nearly 1400 participants
in our studies and performed preliminary genetic analyses that strongly support a significant
genetic susceptibility to MeN, including identification of one set of genetic variants associated
with MeN at genome-wide significance levels. We propose to 1) conduct a case-control
genome-wide association study of former sugar cane workers with MeN and current healthy
workers, 2) study 40 large, multigenerational MeN kindreds using a family-based genetic
approach, and 3) validate our findings and conduct additional SNP discovery in a longitudinal
community-based cohort, as well as in miners and brick makers who are also affected by MeN.
Our study design is optimized to identify genetic risk variants with different combinations of
frequency, effect size, and dependence on environmental interactions. This project will
illuminate genetic risk factors that cause susceptibility to kidney disease in people of mixed
ancestry in our Central American neighbors and may also help us understand mechanisms
that contribute to high rates of kidney disease in other populations with Native American or
Hispanic ancestry.

## Key facts

- **NIH application ID:** 10212372
- **Project number:** 5R01DK116021-04
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** DANIEL R BROOKS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $678,087
- **Award type:** 5
- **Project period:** 2018-09-14 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10212372

## Citation

> US National Institutes of Health, RePORTER application 10212372, Role of Genetic Susceptibility in the Central American Kidney Disease Epidemic (5R01DK116021-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10212372. Licensed CC0.

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