# Safety and Efficacy of Human Clinical Trials Using Kidney-on-a-Chip Microphysiological Systems

> **NIH NIH UG3** · UNIVERSITY OF WASHINGTON · 2020 · $818,669

## Abstract

ABSTRACT
Kidney diseases are an expanding public health problem, currently affecting 37 million people and are the 9th
leading cause of death in the US, while disproportionately accounting for ~27% of Medicare expenditures.
Unfortunately, the number of randomized clinical trials has been fewer than all other specialties of internal
medicine with very low success rates, likely due to the structural and functional complexity of the kidney. The
multicellular architecture and unusual triad of physiological processes characterized by glomerular filtration,
tubular secretion, and tubular reabsorption have limited the ability of animal models to recapitulate the diversity
of etiologies, mechanisms, and heterogenous manifestations of most human kidney diseases. Additionally,
until recently there has been a lack of in vitro models that recapitulate critical aspects of kidney physiology,
mimic the unique complexities of specific nephron segments, or assess reparative mechanisms in response
to injury. In response to this critical unmet need, our group has pioneered the development of `human kidney
on a chip' microphysiological systems (MPS). Our integrated approach for in vitro disease modeling includes
differentiating human kidney cells and organoids from diseased patient-derived inducible pluripotent stem cells
(iPSCs), CRISPR gene editing, single cell transcriptional profiling and engineered MPS platforms for both
living human kidney vascular networks and tubular units. This approach has already led us to achieve new
mechanistic insights into the pathogenesis of autosomal dominant polycystic kidney disease (PKD, the leading
monogenetic cause of kidney failure) and potential new therapeutic pathways. In parallel, significant efforts
led by us are underway in the Nephrotic Syndrome Study Network (known as NEPTUNE) and the Kidney
Precision Medicine Project, NIH funded Consortia designed to address the functional heterogeneity of kidney
disease by rigorous molecular, histologic and phenotypic characterization of kidney diseases. The NCATS
Rare Disease Clinical Network NEPTUNE is testing the precision medicine concept by matching individual
molecular profiles from patients to targeted therapy trials. We now propose to leverage these field-leading
tools to inform clinical trial design and planning, accounting for human genetic and clinical response
heterogeneity for PKD and Focal Segmental Glomerulosclerosis (FSGS), the form of nephrotic syndrome with
the most severe patient consequences. Based on our data, we hypothesize that kidney-on-a-chip MPS will
manifest patient-specific phenotypic responses in vitro commensurate with clinical trial outcomes in vivo,
establishing a robust molecular and cellular basis for kidney precision medicine approaches. We have
established a multidisciplinary investigative team with all the field-leading expertise needed to address all
technical and experimental challenges.

## Key facts

- **NIH application ID:** 10037553
- **Project number:** 1UG3TR003288-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Jonathan Himmelfarb
- **Activity code:** UG3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $818,669
- **Award type:** 1
- **Project period:** 2020-07-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10037553

## Citation

> US National Institutes of Health, RePORTER application 10037553, Safety and Efficacy of Human Clinical Trials Using Kidney-on-a-Chip Microphysiological Systems (1UG3TR003288-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10037553. Licensed CC0.

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