# Angiotensin-Neprilysin Inhibition in Hemodialysis Initiation

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $350,100

## Abstract

PROJECT SUMMARY
Each year over 107,000 patients initiate hemodialysis (HD) for the treatment of advanced kidney failure in the
United States alone. The risk of death is startling, with peak mortality observed during the first two months, most
of which relates to cardiovascular (CV) disease. The majority of incident HD patients are hypervolemic and have
evidence of cardiac structural abnormalities, which are associated with a higher risk of adverse CV outcomes.
Furthermore, patients who lose residual renal function rapidly appear to be at highest risk of adverse outcomes.
 Pharmacologic inhibition of the renin-angiotensin system is known to reduce CV outcomes in non-HD patients
and slow the progression of kidney disease in patients with type 2 diabetes, but these beneficial effects have not
been observed in the HD population. Combining an angiotensin receptor blocker with a neprilysin inhibitor has
been shown to reduce CV outcomes in patients with heart failure, while at the same time slowing the rate of
kidney function decline. Therefore, there is strong biologic rationale to test the effects of this therapy in incident
HD patients.
 Thus, building on our prior data, in we propose a pilot randomized placebo-controlled parallel group clinical
trial to test the safety and tolerability of sacubitril/valsartan and test the effects (vs. placebo) on the reduction of
left atrial volume index and preservation of residual renal function in incident HD patients. The results of our
studies will inform the design and development of a larger multi-center outcomes trial, which is urgently needed
to address the unacceptably high rates of mortality in incident HD.
 In summary, our proposals are clinically relevant, feasible, innovative, and are supported by preliminary data.
Building on the underlying pathophysiology and our experience in performance of clinical trials, our proposals
have the potential to improve care for patients undergoing initiation of HD for kidney failure.

## Key facts

- **NIH application ID:** 10446192
- **Project number:** 1R01DK129749-01A1
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Finnian R McCausland
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $350,100
- **Award type:** 1
- **Project period:** 2022-04-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10446192

## Citation

> US National Institutes of Health, RePORTER application 10446192, Angiotensin-Neprilysin Inhibition in Hemodialysis Initiation (1R01DK129749-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10446192. Licensed CC0.

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