# Mechanisms of Alcohol Toxicity and Kidney Damage

> **NIH NIH R21** · UNIVERSITY OF COLORADO DENVER · 2021 · $223,531

## Abstract

Project Summary
Alcohol consumption contributes to approximately 6% of worldwide deaths. There remains a pressing need for
understanding the biochemical mechanisms underlying alcohol toxicity and kidney disease, as chronic alcohol
ingestion has been shown to play a key role in the development of acute kidney injury associated with the
mortality of alcohol-associated liver disease. It is undeniable that the effect of excessive alcohol consumption
presents a direct route to kidney damage, yet the mechanisms underlying this effect remain unknown. This
proposal integrates key preliminary data into an innovative hypothesis that alcohol metabolism leads to
disrupted acetyl-dependent cellular signaling and altered gene expression profiles, contributing to proximal
tubule damage and kidney disease. Alcohol metabolism is known to alter numerous biochemical pathways
which leads to negative consequences throughout the cell, including altered genetic reprogramming and cell
death. Therefore, alcohol-induced protein acetylation is likely a key initial driver of these changes and
downstream kidney pathologies, such as proximal tubular dysfunction. Therefore, we present an innovative
approach for investigating how alcohol toxicity induces kidney damage. We will investigate the proposed
specific aims: Specific Aim 1: Determine how chronic alcohol consumption alters renal histone acetylation
profiles and gene expression using tissue spatial transcriptomics. Specific Aim 2: Examine altered proximal
tubule pathology and proteomic activity resulting from chronic alcohol metabolism. These aims will be
interrogated utilizing a multidisciplinary approach that will integrate pathological analysis, quantitative mass
spectrometry for proteomics, enzymatic assays, and tissue morphology gene expression, as well as innovative
data analyses and bioinformatics. A key outcome of this research will be an enhanced understanding of the
mechanisms by which alcohol metabolism impacts renal function to further therapeutic intervention and the
amelioration of kidney disease.

## Key facts

- **NIH application ID:** 10371787
- **Project number:** 1R21AA029218-01A1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Kristofer S Fritz
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $223,531
- **Award type:** 1
- **Project period:** 2021-09-25 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371787

## Citation

> US National Institutes of Health, RePORTER application 10371787, Mechanisms of Alcohol Toxicity and Kidney Damage (1R21AA029218-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10371787. Licensed CC0.

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