# Renal Disposition in NASH

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2020 · $482,102

## Abstract

PROJECT SUMMARY
The interrelation between liver disease and kidney function is becoming increasingly researched, as hepatic-
derived systemic inflammation can have a profound effect on the physiology of the kidney. This is a vital factor
to consider with respect to precision medicine, as these changes can disrupt the proper metabolism and
elimination of the 32% of marketed therapeutics that rely upon renal function for excretion. Among the liver
diseases that affect renal physiology is nonalcoholic fatty liver disease (NAFLD), characterized by a series of
mechanistic events that mediate the transition from simple steatosis to nonalcoholic steatohepatitis (NASH),
which include inflammatory events. Our lab has identified NASH-induced phenotypic conversions of several drug
metabolizing enzyme and transport proteins that significantly alter the pharmacokinetic profiles of certain drugs
and xenobiotics. Interestingly, in a profiling study of various rodent models of NASH, we have also identified
NASH-induced phenoconversion of renal transport proteins, a phenomenon that also contributes to altered
pharmacokinetics of xenobiotic substrates in vivo. To date, no studies have been published examining human
NASH-related phenoconversion of renal drug transporters, and that will be the first item we address in this
application. Our central hypothesis is that NASH alters the expression and function of major renal drug
transporters, thereby increasing the risk of adverse drug reactions and environmental toxicities in
patients with NASH. Our study design seeks not only to identify phenoconversion of specific renal transporters
in NASH, but also to pinpoint the associated secretory pathways to better narrow down mechanisms of altered
pharmacokinetics for certain therapeutics and environmental contaminants. Our aims are to: 1) Determine the
changes in expression and localization of renal transporters in human NASH patients, 2) Determine the
functional changes in individual secretion pathways and resulting potential for environmental toxicity in a rodent
model of NASH, and 3) Determine the impact of NASH on GFR and select secretion pathways in human patients.
By completing these aims, we will be able to identify classes of drugs that present a greater risk of adverse drug
events for NASH patients.

## Key facts

- **NIH application ID:** 9852442
- **Project number:** 5R01ES028668-02
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Nathan J Cherrington
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $482,102
- **Award type:** 5
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852442

## Citation

> US National Institutes of Health, RePORTER application 9852442, Renal Disposition in NASH (5R01ES028668-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9852442. Licensed CC0.

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