# Role of DPP4 in Kidney Inflammation and Injury

> **NIH NIH K08** · UNIVERSITY OF MISSOURI-COLUMBIA · 2021 · $169,246

## Abstract

Project Summary/Abstract
The incidence of chronic kidney disease (CKD) is increasing due to the ever-expanding number of people who
are either obese (33%) or diabetic (9%) or both. In a significant proportion of obese-diabetic subjects, CKD may
progress to end stage renal disease (ESRD) and dialysis faster than non-obese diabetic subjects. Care of ESRD
patients (1% of Medicare population) consumes Medicare dollars in a disproportional manner (7%). Hence,
preventing progression of CKD to ESRD is of paramount importance. Currently, the standard of care is to use
medications that block/suppress activation of the renin-angiotensin system. However, these medications are not
enough to stop progression to ESRD in many subjects and novel therapeutic agents are needed. DPP4 inhibitors
are conveniently placed at the intersection of diabetes and CKD due to recent data showing improvement in
proteinuria in diabetic patients with CKD (SAVOR-TIMI trial and animal models). Dr. Nistala and others have
shown that DPP4 inhibitors may have kidney specific effects independent of blood pressure or blood sugar
improvement. However, the mechanisms of DPP4 inhibitor-mediated benefits in the kidney are relatively
unknown. If DPP4 inhibitors are to be used for preventing progression of kidney disease, the biological function
of DPP4 in the kidney needs better understanding. Data supports the notion that DPP4 may regulate sodium
absorption and albumin/oligomeric peptide endocytosis in proximal tubules of the kidney. In addition, DPP4 is a
co-stimulatory molecule for T-lymphocytes, activates mononuclear cells (including macrophages and antigen
presenting cells [APCs]) and may mediate inflammation based on findings from fat depots in obese and plasma
from diabetes patients. Tubulointerstitial inflammation and fibrosis plays an important role in the progression of
CKD in the setting of obesity and diabetes and importantly, Dr. Nistala found that DPP4 activity is increased in
the kidney and expression levels are higher in the proximal tubules of obese/diabetic mice. Therefore, this project
is focused on examining the role of DPP4 in the proximal tubule and kidney immune system in the setting of
obesity/diabetes. The experiments are designed to address the central hypothesis that obesity-
induced proximal tubule DPP4 activation incites a pro-inflammatory immune response leading to
tubulointerstitial fibrosis and progression of kidney disease. To address this hypothesis, DPP4 will be
activated via high sucrose/high fat (Western Diet) feeding in mice with or without DPP4 deficiency. In Aim 1, the
role of Western diet in activation of DPP4 in the proximal tubule and tubular dysfunction will be studied by using
proximal tubule specific deletion of DPP4. In Aim 2, the role of proximal tubule DPP4 in kidney immune system
activation will be examined. In Aim 3, the role of proximal tubule DPP4-induced immune system activation in
tubulointerstitial fibrosis and kidney disease progressio...

## Key facts

- **NIH application ID:** 10087515
- **Project number:** 5K08DK115886-03
- **Recipient organization:** UNIVERSITY OF MISSOURI-COLUMBIA
- **Principal Investigator:** Ravi Nistala
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $169,246
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10087515

## Citation

> US National Institutes of Health, RePORTER application 10087515, Role of DPP4 in Kidney Inflammation and Injury (5K08DK115886-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10087515. Licensed CC0.

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