# Glomerular and Tubular Function in the Diabetic Kidney

> **NIH NIH R01** · VETERANS MEDICAL RESEARCH FDN/SAN DIEGO · 2023 · $485,987

## Abstract

PROJECT SUMMARY ABSTRACT
Inhibitors of the principle kidney glucose transporter, SGLT2, have been shown to slow the progression of
chronic kidney disease (CKD) in the presence or absence of diabetes mellitus. However, major knowledge gaps
remain in how these drugs act on the kidney. Knowledge gaps include how SGLT2 inhibitors alter kidney
microvasculature functions, the tubular system, and kidney metabolism. Features that are observed at the
whole-kidney level emerge from events at the microscopic level and treatments have their direct effect at the
microscopic level. Microscopic behavior, however, cannot be deduced from whole-kidney behavior and must be
observed directly. This cannot be done in humans but can be done in rat and mouse models of human kidney
injury using specialized techniques at which the investigators are expert. By these methods this research will
determine the effects of SGLT2 inhibitors on the inner workings of the kidney. This includes a proposed
relaxation of the efferent arteriole, which may not have any effect on GFR but it always reduces filtration
fraction and increases O2 delivery to the kidney. Studies will determine potential for targeting of SGLT1 as a
new therapeutic strategy to protect the kidney. We will determine whether SGLT2 inhibitors have off-target
effects in the kidney, which have been proposed for the heart. We will compare the metabolomics signature of
these drugs in both experimental and clinical samples. And we aim to delineate the metabolomic and
proteomic signature of these drugs in the very tubular cells they target, i.e., the early proximal tubule, but also
compare these effects with responses in downstream tubular cells exposed to more glucose as a consequence of
drug action. Our goal is an integrated understanding how these drugs impinge on the kidney in the healthy and
diseased kidney to better understand their therapeutic benefits.

## Key facts

- **NIH application ID:** 10660770
- **Project number:** 2R01DK112042-06A1
- **Recipient organization:** VETERANS MEDICAL RESEARCH FDN/SAN DIEGO
- **Principal Investigator:** SCOTT Culver THOMSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $485,987
- **Award type:** 2
- **Project period:** 2017-07-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10660770

## Citation

> US National Institutes of Health, RePORTER application 10660770, Glomerular and Tubular Function in the Diabetic Kidney (2R01DK112042-06A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10660770. Licensed CC0.

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