# GLYCOLATE METABOLISM AND KIDNEY OXALATE

> **NIH NIH K01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $152,604

## Abstract

SUMMARY
 Kidney stones, of which the most common are calcium oxalate (CaOx) stones, affect 7 to 12% of the
United States population and are responsible for 3% of all end-stage renal disease cases. Urine oxalate is
derived from approximately 50% dietary sources and 50% from endogenous synthesis through various
pathways. Though it is well established that approximately 80% of the endogenous oxalate is produced in
the liver, the pathways for oxalate production are not well characterized. Our hypothesis is that glycolate is
a major source of oxalate and that the renal reabsorption of glycolate leads to renal synthesis of oxalate.
Establishing the role of glycolate in renal and liver synthesis of oxalate has implications for patients with the
hereditary disease primary hyperoxaluria (PH), in which excessive endogenous oxalate production leads to
severe recurrent CaOx kidney stones. Establishing these pathways could lead to new treatments to inhibit
glycolate oxidation, resulting in reduced oxalate production.
 This proposal will 1) test if the metabolism of glycolate contributes to endogenous oxalate synthesis by
performing primed, steady state, continuous intravenous infusions of the stable isotope of glycolate, carbon-
13 glycolate, in healthy volunteers. 2) test the hypothesis that glycolate is metabolized to oxalate in proximal
tubule cells using a human proximal tubule cell line and freshly isolated human proximal tubule fragments
and 3) determine renal reabsorption and metabolism of glycolate using isolated rat kidney perfusions. The
roles of the enzyme hydroxyacid oxidase 2 (HAO2) and glyoxylate reductase (GR) will be defined in the
context of this conversion.
 The mentoring team and training plan associated with this proposal will ensure that the candidate
reaches the level of expertise in analytical chemistry, metabolic research, and human and animal studies
that are necessary to meet her goals. The candidate's long-term objective is to lead a strong independent
research program in the field of oxalate metabolism and the clinical disorders associated with it, including
the primary hyperoxalurias.

## Key facts

- **NIH application ID:** 10011568
- **Project number:** 5K01DK114332-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Sonia Fargue
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $152,604
- **Award type:** 5
- **Project period:** 2017-09-05 → 2022-09-04

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10011568

## Citation

> US National Institutes of Health, RePORTER application 10011568, GLYCOLATE METABOLISM AND KIDNEY OXALATE (5K01DK114332-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10011568. Licensed CC0.

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