# Autophagy and Arteriovenous Fistula Maturation

> **NIH NIH R01** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2024 · $527,748

## Abstract

The vascular access is the lifeline for the hemodialysis patient and the single most important
component of the hemodialysis procedure. The most common etiology of vascular access
dysfunction in hemodialysis patients is failure of an arteriovenous fistula (AVF) to mature
successfully for dialysis use (AVF maturation failure). At present, there remains a very high rate of
AVF maturation failure in the United States and there are no effective treatments to enhance AVF
maturation. On a radiologic level, AVF maturation failure is most commonly characterized by a
stenosis at the venous anastomosis, and at a histological level it is characterized by a combination
of aggressive intimal hyperplasia and poor outward remodeling. The poor outcomes following AVF
creation reflect our limited understanding of the mechanisms leading to AVF maturation failure; and
the lack of therapies to treat this clinical problem represent an unmet clinical need. The objective of
this proposal is to investigate a new paradigm, the role of autophagy in AVF maturation. Our
proposal is novel and supported by strong preliminary work from our research team pointing to a
causal role for repressed endothelial cell (EC) autophagy in AVF maturation failure, in response to
a unique setting of disturbed hemodynamics in the AVF and chronic kidney disease (CKD) milieu.
Based on these preliminary studies, the central hypothesis of this proposal is that disturbed flow
and CKD repress endothelial autophagy, leading to AVF maturation failure. Using a combination of
in vitro, in vivo, and, human studies, we will test our central hypothesis with three specific aims: (1)
Identify steps of EC autophagy repression in the setting of disturbed flow and CKD milieu, (2) Define
how repressed EC autophagy contributes to AVF remodeling, and (3) Determine the role of
autophagy in AVF maturation in hemodialysis patients. We believe our proposed research is
significant because: (1) it addressed a very important clinical problem in hemodialysis patients, AVF
maturation failure, where there are presently no effective therapies; and (2) examine a new
paradigm in AVF development, autophagy. Successful completion of these aims will identify
important targets for developing innovative therapies that aim to modify autophagy in order to
enhance AVF maturation.

## Key facts

- **NIH application ID:** 10831413
- **Project number:** 5R01HL153244-04
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** TIMMY C LEE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $527,748
- **Award type:** 5
- **Project period:** 2021-06-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10831413

## Citation

> US National Institutes of Health, RePORTER application 10831413, Autophagy and Arteriovenous Fistula Maturation (5R01HL153244-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10831413. Licensed CC0.

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