# CKDu and Ochratoxin-A: risk assessment studies in a microphysiological system

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2021 · $182,711

## Abstract

Project Summary/Abstract
CKDu (CKD of unknown etiology) occurs primarily in the developing world, and is associated with living and
working in agricultural communities in hot climates. The cost of treating CKDu is unattainable in low-income
countries, where 30 days of essential medications can cost up to 18 days wages. One proposed risk factor of
CKDu is chronic exposure to Ochratoxin A (OTA), a common mycotoxin found in cereal grains, beans, dried
fruits, wine, coffee, and tea. OTA is a demonstrated renal carcinogen in several animal species, however
hazard identification in humans has been elusive due to the lack of adequate models that include hepatic
bioactivation as a source of the ultimate toxic moiety.
We have recently developed a coupled liver>kidney microphysiologic system (MPS) that was used to identify
the specific hepatic enzymes, renal transporters, and intermediate chemical metabolites associated with
aristolochic acid mediated CKDu. Cultured under constant flow, primary liver and kidney cells demonstrated
localized phase-I/II enzymes and transporters, a significant advance over immortalized cell lines that rapidly
lose enzyme expression and transporter polarization. In addition, primary kidney proximal tubule cells exhibited
robust and biomimetic secretion of biomarkers of kidney injury.
For this proposal, we have developed an innovative integrated liver>kidney MPS that incorporates both a
coupled and uncoupled kidney MPS on a single chip. We propose to define the dose-response relationships of
ochratoxin A and heat stress-induced nephropathy, identify the transport proteins involved in renal ochratoxin
A uptake and efflux, and determine the role of first pass metabolism in ochratoxin A-induced nephropathy. A
better understanding of the mechanisms of OTA-induced kidney injury will support changes in risk assessment,
regulatory agency policies on allowable exposure levels, and determination of genetic risk factors in high-risk
populations.

## Key facts

- **NIH application ID:** 10197129
- **Project number:** 5R21ES031359-02
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** EDWARD J KELLY
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $182,711
- **Award type:** 5
- **Project period:** 2020-06-17 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10197129

## Citation

> US National Institutes of Health, RePORTER application 10197129, CKDu and Ochratoxin-A: risk assessment studies in a microphysiological system (5R21ES031359-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10197129. Licensed CC0.

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