# Intestinal oxalate transport and the regulation of the apical Slc26 anion exchangers involved

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2020 · $469,731

## Abstract

Abstract
 Hyperoxaluria is a major risk factor in the development of calcium oxalate kidney stone disease which
presently occurs in about 12% of the American population, costing an estimated $2 billion annually. Despite
the significant and serious clinical consequences of hyperoxaluria, which can be associated with numerous
diseases and conditions, including an emerging population of patients who undergo gastric bypass surgery,
there is still no effective pharmacological treatment to resolve this problem. Consequently, patients have to
resort to invasive procedures to eliminate kidney stones and/or suffer the ramifications, including the possibility
of renal failure and even death.
 Several key pieces of information obtained from our studies over the years have supported the notion that
a significant amount of the body burden of oxalate can be eliminated through the intestinal tract resulting in
reduced amounts of oxalate passing through the kidneys. This basic proof of principle was demonstrated
earlier in rats with chronic renal failure where urinary oxalate was reduced 50 % due to the induction of enteric
oxalate elimination. In addition, we demonstrated that a mouse model with elevated concentrations of oxalate
in the blood and urine, due to the genetic disease of Primary Hyperoxaluria, type 1, were normalized by enteric
oxalate excretion being initiated in the presence of the probiotic bacterium, Oxalobacter sp.
 Hence, there exists considerable interest in exploiting the intestine as a means of alleviating the systemic
oxalate load to mitigate the risk of stone formation and the eventual consequences of this kidney disease. The
investment in furthering this beneficial approach involves a more in-depth look at the pathways oxalate utilizes
to cross the intestinal barrier, and specifically, how they are regulated. While we have been steadily
developing an understanding about the proteins involved, which belong to the Slc26 gene family, we cannot
currently explain how these transporters are regulated in the different segments of the intestine. Based upon
some very provocative preliminary data, we have established a research plan with two comprehensive,
integrated Specific Aims The strength of this research strategy comprises a number of innovative approaches
coupled with a solid, feasible experimental design in a concerted effort to determine two major “unknowns”; (i)
how the components of the bicarbonate-buffering system (pH, CO2 and HCO3- in conjunction with carbonic
anhydrase), and (ii) how the cAMP-dependent regulatory pathways modulate net oxalate secretion and the
enteric elimination of oxalate. This knowledge will represent a crucial step toward realizing the therapeutic
potential of the intestine for resolving hyperoxaluria.
1

## Key facts

- **NIH application ID:** 9873025
- **Project number:** 5R01DK108755-04
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Marguerite Hatch
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $469,731
- **Award type:** 5
- **Project period:** 2017-03-17 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9873025

## Citation

> US National Institutes of Health, RePORTER application 9873025, Intestinal oxalate transport and the regulation of the apical Slc26 anion exchangers involved (5R01DK108755-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9873025. Licensed CC0.

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