# Evaluating the Mechanisms of Afferent Renal Nerve Ablation as a Treatment for Hypertension

> **NIH NIH F30** · UNIVERSITY OF MINNESOTA · 2024 · $49,324

## Abstract

PROJECT SUMMARY/ABSTRACT
Hypertension (HTN) is one of the most important risk factors for cardiovascular disease. Nearly half of HTN
patients are resistant or nonadherent to lifestyle modification and drug-based therapy, so novel therapies are
desperately needed. While HTN is associated with increased global sympathetic nerve activity, renal efferent
nerves have traditionally been the focus of research since they transmit sympathetic nerve impulses from the
brain to regulate blood pressure. However, the kidneys are also innervated by renal afferent (sensory) nerves,
which project to circuits in the brain that modulate sympathetic nerve output and cause HTN. Clinical trials using
catheter-based total (efferent and afferent) renal nerve ablation (TRDN) have been shown to effectively lower
arterial pressure in treatment-resistant HTN patients. Despite this intervention’s efficacy, it is unknown if ablation
of the efferent or afferent renal nerves is more important in lowering arterial pressure. To elucidate the role that
afferent renal nerves play in HTN, our laboratory developed a novel method of afferent renal nerve ablation
(ARDN) and found that ARDN was as effective as TRDN in decreasing arterial pressure in the
deoxycorticosterone acetate and high salt diet (DOCA-salt) induced HTN rodent model. Clinically, if ARDN can
lower arterial pressure to the same degree as TRDN, efferent renal nerves could be preserved to maintain blood
pressure and volume in response to hemorrhagic or septic shock. Furthermore, TRDN has shown variable
efficacy in certain patients, and the lack of biomarkers to predict the arterial pressure response to TRDN is a
major gap in the field. Recent studies from our lab suggest that the presence of specific inflammatory cytokines
in the urine can identify renal inflammation. These cytokines can overstimulate afferent renal nerves and cause
increased global sympathetic nerve output and HTN. I plan on translating our findings from DOCA-salt HTN
rodents to the DOCA-salt HTN sheep model. The anatomic, physiologic, and hemodynamic properties of HTN
sheep more closely resemble human pathophysiology and allows for the use of human TRDN catheters.
Therefore, the overall goal of this proposal is to develop and validate a catheter-based ARDN method using the
HTN sheep model to address current gaps in the field and move closer to a clinical therapeutic for hypertension.
Our central hypothesis is that catheter-based ARDN will decrease arterial pressure to the same degree as TRDN,
and the arterial pressure response to TRDN can be predicted by specific urinary markers of renal inflammation.
I will test this hypothesis with the following aims: (1) Compare the efficacy of catheter-based ARDN versus TRDN
in an established model of HTN in sheep. (2) Validate the utility of urinary biomarkers to measure renal
inflammation associated with HTN to predict the anti-HTN efficacy of TRDN. If successful, the results of the
proposed studies will provide ...

## Key facts

- **NIH application ID:** 10917044
- **Project number:** 5F30HL167564-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Arthur Trenton de la Cruz-Lynch
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $49,324
- **Award type:** 5
- **Project period:** 2023-09-01 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10917044

## Citation

> US National Institutes of Health, RePORTER application 10917044, Evaluating the Mechanisms of Afferent Renal Nerve Ablation as a Treatment for Hypertension (5F30HL167564-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10917044. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*
