# Dietary Oxalate and Innate Immunity in Kidney Stone Disease

> **NIH NIH R03** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $108,186

## Abstract

PROJECT SUMMARY:
Kidney stone (KS) disease is becoming more prevalent in the United States and is associated with systemic
diseases and lifestyle factors such as diet. A major risk factor for stone formation is an elevation in urinary
oxalate, which can be derived endogenously or from the diet. Dietary oxalate intake may induce
supersaturation of calcium oxalate (CaOx) which may generate crystals of this stone forming salt in urine and
perhaps the nephron. CaOx crystals that interact with renal epithelium activate innate immunity by releasing
cytokines and chemokines to stimulate monocyte recruitment. We previously reported that patients with CaOx
kidney stone (CaOx KS) disease have altered monocyte cellular energetics and increased inflammation. In
addition, we have shown oxalate directly disrupts cellular energetics and redox homeostasis in monocytes from
healthy subjects. The long-term goal of this research is to understand how oxalate impacts monocyte and
macrophage immunometabolism in KS disease. The objective of the current study is to investigate the
relationship between urinary crystals, macrophage activation, reactive oxygen species (ROS), and pro-
inflammatory signaling pathways following oxalate consumption. The central hypothesis is oxalate disrupts
mitochondrial complex I activity in monocytes and stimulates ROS generation, pro-inflammatory macrophage
differentiation, and renal crystal deposition in CaOx KS disease. Aim 1 will test the hypothesis that oxalate
stimulates reverse electron transport (RET) through mitochondrial complex I in monocytes from healthy
subjects. Aim 2 will test the hypothesis that oxalate mediated crystalluria induces ROS and disrupts
macrophage immunometabolism in rat kidneys. No studies to date have investigated the connection between
dietary oxalate, crystalluria, and immune responses in CaOx KS disease. A novel approach to assess urinary
nanocrystals and their influence on monocytes and macrophages will be investigated. The impact of this
research will help us understand how monocytes and macrophages respond to crystals, and may identify
potential approaches to assess stone risk, reduce stone formation, and stone recurrence. The data generated
from this proposal will advance our knowledge about the role of dietary oxalate on immune cells in KS disease
and serve as a key foundation for subsequent R01 funding.

## Key facts

- **NIH application ID:** 9874842
- **Project number:** 1R03DK123542-01
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Tanecia R Mitchell
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $108,186
- **Award type:** 1
- **Project period:** 2020-02-28 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9874842

## Citation

> US National Institutes of Health, RePORTER application 9874842, Dietary Oxalate and Innate Immunity in Kidney Stone Disease (1R03DK123542-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9874842. Licensed CC0.

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