# Chronic kidney disease of unknown etiology: applying a multidisciplinary approach to investigate the world's most common tubulointerstitial kidney disease

> **NIH NIH R01** · STANFORD UNIVERSITY · 2021 · $570,541

## Abstract

PROJECT SUMMARY/ABSTRACT
Over the last twenty years, an increasing number of agricultural communities have faced an apparently new,
unexplained, and fatal kidney disease, known as chronic kidney disease of unknown etiology (CKDu). First
noted in sugar cane workers in El Salvador and rice farmers in Sri Lanka, reports of a similar kidney disease
have emerged come from Nicaragua, Costa Rica, Guatemala, India, and (most recently) the U.S. Despite the
scale and severity of this kidney disease epidemic, the epidemiological and mechanistic investigations needed
to address it have been extremely limited. Because persons with the disease are otherwise healthy agricultural
workers, many experts and the affected population suspect agrochemical exposure is responsible. In two key
preliminary studies from Sri Lanka, we find that agricultural workers are drinking from shallow water wells that
are contaminated by organophosphate and organochlorine agrochemicals above EPA drinking water
regulations, and well water consumption raises likelihood of biopsy-proven CKDu and faster progression of
established kidney disease. In a cohort of 600 at-risk participants identified by our preliminary work in whom
we will obtain baseline environmental samples including water samples and kidney biopsies if they meet a
validated clinical definition of CKDu, we propose to examine the hypothesis that specific agrochemicals
contaminating well water are causing CKDu. We will: 1) run untargeted and targeted mass spectrometry
analysis of well water, 2) determine the association of individual agrochemicals and their mixtures with incident
CKDu case status, accounting for work intensity and heat stress, 3) measure the bioburden of nephrotoxic
agrochemicals in cases versus controls, and 4) perform molecular analyses of early-stage kidney biopsies to
specify the injury response pattern at a cellular level with bulk and single-cell RNA sequencing. In alignment
with NIDDK-NIEHS-Fogarty recommended approach to CKDu investigations, this proposal integrates a multi-
disciplinary, multi-national team of nephrologists, pathologists, molecular biologists and environmental
geochemists. Based on our preliminary data we focus on agrochemical exposure via well water as the
environmental risk factor of interest in this proposal, however field work will be coupled with an extensive
biobanking effort to facilitate testing of multiple candidate hypotheses. The complementary molecular analyses
will precisely characterize the injury in CKDu in the context of other primary tubulointerstitial kidney diseases,
and create a rigorous scaffold for testing potential agents that can trigger CKDu-specific responses in the
kidney. As in the case of prior regional kidney disease epidemics such as Balkan nephropathy, the intensive
effort to identify cause in our outlined aims has the potential to pinpoint other vulnerable populations and
regions, and more importantly, to abrogate the kidney disease by eliminating the...

## Key facts

- **NIH application ID:** 10100433
- **Project number:** 1R01DK127138-01
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Shuchi Anand
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $570,541
- **Award type:** 1
- **Project period:** 2021-01-28 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10100433

## Citation

> US National Institutes of Health, RePORTER application 10100433, Chronic kidney disease of unknown etiology: applying a multidisciplinary approach to investigate the world's most common tubulointerstitial kidney disease (1R01DK127138-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10100433. Licensed CC0.

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