# Role of TRPV1 renal sensory nerves in chronic kidney disease

> **NIH NIH K99** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $91,500

## Abstract

ABSTRACT
CKD is characterized by irreversible kidney damage, worsening renal function, and sympathetic
activation. Renal nerve denervation improves kidney function in CKD patients. These effects are
partly attributed to altered renal afferent (sensory) nerve activity (ARNA). Renal sensory nerves
sense changes in the chemical milieu of the kidney and reflexively modulate sympathetic outflow
to maintain kidney homeostasis. The pathogenic contribution of renal sensory nerves in the
development of CKD is poorly defined. TRPV1 channels are expressed in renal sensory nerves
and the TRPV1 agonist capsaicin increases ARNA and renal sympathetic nerve activity. TRPV1
is a nonselective cation channel that responds to noxious stimuli, pH, and chemokines. Moreover,
persistent inflammation is a pathologic hallmark of CKD and TRPV1 channels promote
inflammation in experimental models of pain and nephropathy. Therefore, my core hypothesis
is that TRPV1-expressing renal afferent nerves are overactive and sensitized in CKD to
subsequently elevate renal SNA and reduce GFR. Chronically, TRPV1-expressing renal
afferent fibers sense renal cytokines and contribute to renal inflammation that further
elevate renal SNA and reduces GFR–worsening CKD progression. This hypothesis will be
tested using “state-of-the-art” neurophysiological approaches and novel TRPV1-flox and TRPV1-
Cre transgenic rat lines. Single unit recordings and single-cell transcriptomics will be employed in
parallel to examine the identity of TRPV1 and non-TRPV1 expressing neurons and link them with
their activity in CKD. Optogenetics and transgenic rats will be used to test the extent by which
TRPV1-expressing renal sensory fibers or TRPV1 channels influence renal efferent SNA and
renal function in CKD. Lastly, renal cytokine-evoked ARNA responses will be evaluated and their
impact on renal SNA and renal hemodynamics will be tested. Completion of these aims will 1)
identify novel renal sensory nerve populations that directly contribute to renal dysfunction
and inflammation in CKD and 2) provide support for establishing an independent research
program focused on the neural control of kidney function in renal disease such as CKD.

## Key facts

- **NIH application ID:** 10506625
- **Project number:** 1K99DK133561-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Leon Joseph DeLalio
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $91,500
- **Award type:** 1
- **Project period:** 2022-09-01 → 2023-06-10

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10506625

## Citation

> US National Institutes of Health, RePORTER application 10506625, Role of TRPV1 renal sensory nerves in chronic kidney disease (1K99DK133561-01). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10506625. Licensed CC0.

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