# Redefining the limits of tolerable warm ischemia in deceased donor kidneys

> **NIH NIH R21** · YALE UNIVERSITY · 2022 · $251,250

## Abstract

PROJECT SUMMARY
In spite of significant effort to expand the pool of organ donors, there remains a severe gap between the supply
of organs and the number patients in need of a living saving transplant. The persistence and sheer magnitude
of this issue suggests the need for a disruptive new approach that can fundamentally change the paradigm of
organ donation. We propose to achieve this paradigm shift by developing new organ perfusion technology that
can transform donor eligibility criteria to allow for donation after death in an uncontrolled setting outside of the
hospital. At current, only 0.7% of organ donors that die in a given year will have their organs actually recovered.
A major contributing factor to this low percentage is the requirement that donors must die in a controlled hospital
setting to facilitate rapid organ recovery that ensures <1 hr of warm ischemia. If this tolerable warm ischemic
time could be expanded to ~3 hrs or more, this would make it logistically feasible to allow for donation after death
in uncontrolled settings such as cardiac arrest on the way to the hospital. This could dramatically increase the
number of donor organs available, particularly following sudden cardiac arrest. We have recently shown in two
independent studies of human kidney and pig brain, that ex vivo organ perfusion with the appropriate therapeutic
perfusate can access a previously unappreciated resilience to ischemic injury. Based on this, we hypothesize
that an appropriately designed perfusion system will be capable of restoring stable renal function ex vivo in
kidneys after at least ~3 hrs of warm ischemia. To this end, we have developed a novel perfusion approach
which combines an acellular cytoprotective perfusate paired with a custom perfusion system capable of
continuous physiologic monitoring and real-time integrated organ support. Instead of red blood cells, our
perfusate uses polymerized hemoglobin to enable oxygen delivery under a range of perfusion temperatures and
avoid the complications of hemolysis. In this proposal, we will refine and test the capacity of our novel approach
to mitigate two critical modes of failure following 3 hrs of warm ischemia: 1) Severe ATP depletion with related
disruption of the electron transport chain (ETC); and 2) Dysfunctional inflammation induced by regulated necrosis
after reperfusion. Successful completion of this project will establish new technology with the potential to
transform our definition of what constitutes an eligible organ donor.

## Key facts

- **NIH application ID:** 10368145
- **Project number:** 5R21DK128662-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Gregory T Tietjen
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $251,250
- **Award type:** 5
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10368145

## Citation

> US National Institutes of Health, RePORTER application 10368145, Redefining the limits of tolerable warm ischemia in deceased donor kidneys (5R21DK128662-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10368145. Licensed CC0.

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