# Oxalate-Driven Host Responses in Kidney Stone Disease

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2023 · $550,243

## Abstract

PROJECT SUMMARY/ABSTRACT
Kidney stones (KS) are painful mineral deposits that affect 1 in 11 individuals in the United States. The economic
burden from KS is over $5 billion dollars annually and is predicted to rise due to increasing prevalence.
Approximately 80% of KS are comprised of calcium oxalate (CaOx). Several individuals with CaOx KS develop
recurrent KS. The reasons for recurrence are not well defined. Intake of meals containing high amounts of oxalate
are associated with increased KS risk. Oxalate-rich diets may induce CaOx crystal formation in the urine and
nephron, which can stimulate reactive oxygen species signaling and monocyte recruitment into the renal
interstitium. If crystals are not properly cleared by macrophages, this could result in the propagation of KS.
Interleukin-10 (IL-10) is a key anti-inflammatory cytokine important for regulating monocyte and macrophage
function. We previously reported patients with CaOx KS have reduced circulating monocyte cellular
bioenergetics and increased inflammation. We further determined that CaOx crystals can cause similar
responses in monocytes in vitro. We recently reported that intake of a single dietary oxalate load stimulates
nanocrystalluria and alters circulating monocyte cellular bioenergetics in a small cohort of healthy subjects. The
goals of this proposal are to examine the effects of low and high oxalate diets on nanocrystalluria and immunity
using human translational studies and experimental models. The central hypothesis of this proposal is oxalate
suppresses IL-10 signaling leading to reduced cellular bioenergetics, redox homeostasis, and mitochondrial
quality control in macrophages. We further propose this contributes to impaired macrophage clearance of CaOx
crystals from the kidney which may play a role in KS formation. Aim 1 will test the hypothesis that oxalate
enriched diets stimulate nanocrystalluria and reduce monocyte cellular bioenergetics in healthy subjects and
patients with CaOx KS. Aim 2 will test the hypothesis that oxalate reduces IL-10 signaling, cellular bioenergetics,
and mitochondrial quality control in macrophages. This project involves an interdisciplinary team and
multifaceted approaches to assess the effect of oxalate on nanocrystalluria and IL-10-mediated
monocyte/macrophage immune responses, which may play a role in CaOx KS formation. The results obtained
will generate new insights into the cellular mechanisms driving KS formation and should unveil novel strategies
for KS prevention.

## Key facts

- **NIH application ID:** 10692818
- **Project number:** 5R01DK129885-02
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Tanecia R Mitchell
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $550,243
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10692818

## Citation

> US National Institutes of Health, RePORTER application 10692818, Oxalate-Driven Host Responses in Kidney Stone Disease (5R01DK129885-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10692818. Licensed CC0.

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