# Monocyte Mitochondrial Dysfunction and Kidney Stone Disease

> **NIH NIH K01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $153,457

## Abstract

Project Summary/Abstract
 Approximately 9% of the United States population will develop a kidney stone in their lifetime. Lifestyle
factors, genetics, and diet all contribute to the development of kidney stones. The most common type of kidney
stone is comprised of calcium oxalate (CaOx) crystals. Research on kidney stones is hampered by limited
access to kidney cells and tissue from patients. Very few studies have focused on circulating immune cells
which may play a role in disease processes. Monocytes/macrophages are essential for crystal clearance and
are recruited to the renal interstitium. We recently determined that monocytes but not lymphocytes or platelets
have lower mitochondrial function in patients with CaOx kidney stones compared to healthy subjects. The
objective of the current proposal is to evaluate for changes in mitochondrial function, oxidative stress, and
inflammatory responses in circulating monocytes and plasma from a large cohort of patients with CaOx kidney
stones and healthy subjects. This may identify specific responses associated with this disease. The central
hypothesis of the current proposal is circulating monocytes in patients with CaOx kidney stones develop
mitochondrial dysfunction due to cellular events mediated by CaOx stones and/or exposure to CaOx crystals in
the nephron. This hypothesis will be tested by pursuing three specific aims: 1) Determine whether
mitochondrial dysfunction, oxidative stress, and inflammation are associated with circulating monocyte
subtypes in patients with CaOx kidney stones; 2) Elucidate whether cytokines or CaOx crystals induce NLRP3
inflammasome pathways and mitochondrial dysfunction in primary monocytes and a human derived monocyte
cell line; and 3) Determine whether a dietary oxalate load that produces urinary CaOx crystals in healthy
subjects causes similar monocyte responses to those observed in patients. The proposed studies may provide
new insights regarding the role of monocyte function and inflammation in CaOx kidney stone disease. This
research plan will allow the applicant to gain additional experience in kidney stone disease and clinical
research plus training in mass spectrometry, renal pathophysiology, immunology, and biostatistics through
practical experience, course work, and guidance from an experienced mentoring team. It will also advance and
facilitate the success of the applicant to transition into becoming an independent and productive NIH-funded
investigator focused on monocytes and kidney stone disease.

## Key facts

- **NIH application ID:** 9963203
- **Project number:** 5K01DK106284-05
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Tanecia R Mitchell
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $153,457
- **Award type:** 5
- **Project period:** 2016-09-15 → 2022-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9963203

## Citation

> US National Institutes of Health, RePORTER application 9963203, Monocyte Mitochondrial Dysfunction and Kidney Stone Disease (5K01DK106284-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9963203. Licensed CC0.

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