# OXGR1 in Renal Intercalated Cells, Salt Transport and Diuretic Efficacy

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $825,023

## Abstract

Thiazides are one of the most cost-effective and medically beneficial first line
antihypertensive agents. However, they don’t work for everyone, and in some
patients they may lower blood pressure for a while but then wear off. The
mechanisms responsible for thiazide resistance have been mysterious, until
recently. Our recent systems-biology investigations revealed a salt-transport
process is activated by a novel mechanism to limit urinary salt wasting when
NCC, the thiazide target, is inhibited or hypokalemic intravascular volume
depletion occurs. We discovered that a salt reabsorption pathway is created by
the coordinate induction of a multi-gene transport system in non-α intercalated
cells, highlighting the Cl/HCO3- exchanger, pendrin, alpha-ketoglutarate (α-KG)
and the α-KG G-Protein Coupled Receptor, OXGR1. Our recently published and
preliminary data strongly suggest that paracrine delivery of α-KG stimulates
OXGR1 in non-α cells and this activates pendrin, stimulates salt reabsorption,
and potentially lowers the diuretic response. Here, we have assembled a highly
collaborative, multidisciplinary team to rigorously test the central tenants of the -
KG /OXGR1/pendrin hypothesis (Aim 1), explore the underlying molecular
mechanism(s) linking OXGR1 to pendrin activation (Aim 2), elucidate the
physiological stimuli and consequences of the Renal α-KG/OxGR1 Paracrine
system (Aim 3), building on our recent discoveries. We expect these
investigations will have a major impact on understanding how the kidney controls
salt balance in health and disease, in ways that illuminate the central
underpinnings of the variable diuretic response. Ultimately, these studies will
provide new information and diagnostic tools that lead to the better treatment of
hypertension.

## Key facts

- **NIH application ID:** 9913504
- **Project number:** 5R01DK110375-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Eric J Delpire
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $825,023
- **Award type:** 5
- **Project period:** 2019-10-05 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9913504

## Citation

> US National Institutes of Health, RePORTER application 9913504, OXGR1 in Renal Intercalated Cells, Salt Transport and Diuretic Efficacy (5R01DK110375-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9913504. Licensed CC0.

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