# Catheter-associated molecular patterns and arteriovenous fistula failure

> **NIH NIH R21** · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · 2024 · $191,875

## Abstract

PROJECT SUMMARY/ABSTRACT:
Over 700,000 Americans live with end-stage kidney disease (ESKD) and more than 1 million are projected for
2030. Ninety percent of these patients depend on a functional vascular access for hemodialysis (HD) treatments.
However, the high rate of failure and complications of HD accesses is one of the most common causes of
morbidity in this vulnerable population. Approximately 70% of new ESKD patients initiate HD with a central
venous catheter (CVC), and most continue on a catheter for the next 6 months despite the high risk of life-
threatening bloodstream infections. One of the factors contributing to prolonged CVC use is the high rate of
arteriovenous fistula (AVF) maturation failure. Up to 50% of newly created AVFs fail to mature independently
due to significant stenoses (narrowing) in the venous segment. Interestingly, prior CVC use is significantly
associated with AVF maturation failure. In this proposal, I will challenge the high-risk, high-reward hypothesis
that AVF maturation failure after CVC use has a preventable immunological basis. Namely, this discovery and
mechanistic proposal aims to demonstrate the mechanistic link between CVC-derived molecular patterns,
exaggerated activation of neutrophils, and increased vascular damage in newly created fistulas. This proposal
is built on strong scientific premises, including the increased expression of at least 20 neutrophil enriched genes
in human veins that failed compared to veins that remodeled successfully after AVF creation. I hypothesize that
activation of the FPR1 receptor by catheter-derived bacterial peptides primes circulating neutrophils prior to AVF
creation, increases vascular infiltration, and causes an overresponse to postoperative vascular injury that
contributes to AVF failure. The proposal is organized in three complementary Specific Aims (SA). A discovery
SA will look for CVC-related changes in peripheral neutrophils of patients undergoing surgery for AVF creation
using single-cell RNA sequencing. A mechanistic SA will dissect the role of catheter derived N-formylated
peptides in neutrophil activation, and the consequences of this inflammatory pathway for postoperative AVF
remodeling using genetically modified animal models. Lastly, a pre-clinical translational SA will create a
relevant animal model that combines CVC insertion, biofilm formation, and AVF creation, and test the efficacy of
FPR1 activation blockers and neutrophil-depleting therapies to improve AVF remodeling. Considering the
frequent use of catheters in HD patients, results from this grant may not only be significant for AVF maturation
outcomes but also for other postsurgical scenarios such as transplant injury. From the career development
point of view, this application responds to Funding Opportunity Announcement PAR-21-313, which aims at
facilitating the transition of new investigators of diverse and underrepresented backgrounds such as myself to
research independence. This proposal ...

## Key facts

- **NIH application ID:** 10789014
- **Project number:** 1R21DK138390-01
- **Recipient organization:** UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
- **Principal Investigator:** Laisel Martinez
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $191,875
- **Award type:** 1
- **Project period:** 2024-01-22 → 2026-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10789014

## Citation

> US National Institutes of Health, RePORTER application 10789014, Catheter-associated molecular patterns and arteriovenous fistula failure (1R21DK138390-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10789014. Licensed CC0.

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