# A Microphysiological System for Kidney Disease Modeling and Drug Efficacy Testing

> **NIH NIH UH3** · UNIVERSITY OF WASHINGTON · 2021 · $1,174,809

## Abstract

Project Summary
Chronic kidney disease is a public health problem affecting more than 20 million people in the US adult
population, and is the 9th leading cause of death. Few drugs other than renin-angiotensin system inhibitors
slow the progression of kidney disease, lower mortality rates, or improve quality of life among people. New
strategies targeting the early stages of these underlying diseases are fundamentally important to improve
outcomes and patient care. To catalyze the development of drugs that are safe and effective for treating
kidney diseases, there is a critical need to be able to model human kidney diseases and injury in vitro during
preclinical drug development. The complex multicellular architecture and unusual triad of physiological
processes characterized by glomerular filtration, tubular secretion and tubular reabsorption, have often
limited the ability of whole organism models to fully recapitulate the diversity and manifestations of human
disease. Conventional two-dimensional human epithelial cell models do not accurately recapitulate kidney
physiology or disease, and microfluidic flow is essential to kidney nephron structure and function, and is an
essential component in recapitulating in vivo physiology and pathophysiology. We have developed a three
dimensional flow directed “kidney-on-a-chip” microphysiological system populated with human kidney cells,
which has been extensively tested with functional characterization of key component structures of the
proximal tubule and the peritubular microvascular network. We are also able to routinely obtain, isolate and
characterize relatively pure primary cultures of multiple human kidney cell lineages. In addition, we have
developed hydrogels consisting of decellularized human kidney cortical extracellular matrix, and
demonstrated phenotypic differences when human kidney cells are grown in this matrix. In addition, we have
recently incorporated the use of human pluripotent stem cells coupled with gene editing techniques into our
MPS. Our platforms allow for precise control of cellular composition, extracellular matrix, and vascular and
tubular geometry and flow. The goal of this application is to model important human kidney diseases and
promote identification of safe and effective treatments. To achieve this goal, we have established a
multidisciplinary investigative team with expertise in kidney physiology and pathology, cellular and molecular
biology, systems pharmacology and toxicology, biomarker discovery and evaluation, biomedical engineering,
microfluidics, matrix biology, genomics, computational biology, and biostatistics. If successful, ultimately in
vitro models that recapitulate critical aspects of kidney physiological function, response to injury, and repair
could contribute greatly to drug discovery and development, and could ultimately enable `virtual clinical trials'
for candidate therapeutics.

## Key facts

- **NIH application ID:** 10207822
- **Project number:** 5UH3TR002158-05
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Jonathan Himmelfarb
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,174,809
- **Award type:** 5
- **Project period:** 2017-07-25 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10207822

## Citation

> US National Institutes of Health, RePORTER application 10207822, A Microphysiological System for Kidney Disease Modeling and Drug Efficacy Testing (5UH3TR002158-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10207822. Licensed CC0.

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