# Development of a Treatment to Improve Arteriovenous Fistula Function

> **NIH NIH R44** · PAVAJ VASCULAR CORPORATION · 2024 · $499,890

## Abstract

Project Summary/Abstract:
In 2017, there were ~750,000 US patients with end-stage kidney disease (ESKD) who required chronic
hemodialysis (HD). The ESKD population in the USA is increasing at the rate of 3% per year. Vascular access
through an arteriovenous fistula (AVF) is required for optimal HD and clearance of uremic toxins. The patency
of AVFs at one year is estimated to be only 62%. Venous stenosis, which occurs because of venous neointimal
hyperplasia (VNH), is responsible for the majority of AVF failures. Over three billion dollars are spent annually to
maintain the function of hemodialysis AVFs. There are no therapies which can prevent AVF VS. Effective, non-
invasive methods that reduce AVF venous stenosis would be of tremendous benefit to patients with ESKD.
Pavaj Vascular is developing and commercializing a novel therapy that can prevent AVF venous stenosis. We
have published data showing that VS/VNH in AVF is associated with increased expression of immediate early
response genes (Iex-1/Ier3) in clinical specimens with failed HD AVFs. Experimentally, Iex-1-/- mice (genetic
engineered animals that lack Iex-1) with AVFs have less VS/VNH than control mice. Iex-1 expression is down-
regulated by the calciotropic hormone, 1,25(OH)2D3 (1,25), the active form of Vitamin D3, which is used in CKD
patients for calcium homeostasis. Oral administration of 1,25 vitamin D3 does not reduce AVF VS and does
cause hypercalcemia. Adventitial delivery of nanoparticles composed of poly (lactic-co-glycolic acid (PLGA)
encapsulated with 1,25(OH)2D3 (1,25 NP) in a thermosensitive hydrogel to the AVF outflow vein reduces VS/VNH
in mice and pigs with chronic kidney disease (CKD) without hypercalcemia. Furthermore, we have shown that in
mice and pigs, adventitial delivery of 1,25 NP reduces Iex-1 expression and increases blood flow by reducing
VNH. These data suggest that 1,25 NP may be a useful treatment for improving maturation and preventing
VS/VNH in AVF.
Pavaj Vascular will use the direct phase II SBIR to complete two main goals:
1) Evaluate the Stability and Biocompatibility of GMP grade 1,25 NP.
2) Determine the long-term efficacy of 1,25 NP on reducing AVF VS/VNH using a porcine model with CKD.
Successful completion of this proposal will allow us to obtain data needed to apply for FDA Investigational New
Drug (IND) approval to perform First in Man studies to evaluate this promising technology.
.

## Key facts

- **NIH application ID:** 10919089
- **Project number:** 1R44DK139817-01
- **Recipient organization:** PAVAJ VASCULAR CORPORATION
- **Principal Investigator:** Aaron Miller
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $499,890
- **Award type:** 1
- **Project period:** 2024-09-18 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10919089

## Citation

> US National Institutes of Health, RePORTER application 10919089, Development of a Treatment to Improve Arteriovenous Fistula Function (1R44DK139817-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10919089. Licensed CC0.

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