# Mechanisms and Ex Vivo Repair of Cold-Storage Injury in Human Kidney Allografts

> **NIH NIH R01** · YALE UNIVERSITY · 2021 · $509,756

## Abstract

PROJECT SUMMARY
The average duration of cold-storage for deceased-donor kidneys in the U.S. can range from ~9 to >30 hrs in
the U.S. depending on geographic location. It is well established that the longer a kidney is stored cold prior to
transplant, the greater the likelihood of post-transplant complications like delayed graft function. This is
particularly true for organs from aging donors or donors with co-morbidities—an ever-expanding proportion of
the U.S. donor pool—which display increased sensitivity to injury during cold storage. Little is known about the
mechanisms that determine the rate and extent of cold-storage injury in human organs. This lack of knowledge
presents a critical barrier to the development of therapeutic strategies to reduce the clinical impact of cold-storage
injury. We have recently discovered that cold storage induces human kidneys to produce fibrinogen within renal
tubular cells. Upon restoration of normothermia/normoxia, fibrinogen is secreted into the vasculature where it
can aggregate erythrocytes in a rouleaux formation leading to pathologic plugging of microvessels. We
hypothesize that renal fibrinogen is a major effector of cold-storage injury and therefore represents a viable target
to improve organ resilience after cold storage. Ex Vivo Organ Perfusion (EVOP) has emerged as a research and
clinical platform providing an opportunity to directly test this hypothesis in a translationally relevant setting. Here,
we will exclusively use human tissues to achieve two objectives: 1) Determine the mechanism by which cold-
storage induces renal fibrinogen synthesis; and 2) Evaluate EVOP as a therapeutic platform to ameliorate
fibrinogen-mediated pathology pre-transplant. Successful completion of these objectives will establish a new
paradigm for prevention of cold-storage-induced organ injury with the potential to save patient lives by improving
both access to organs and post-transplant outcomes.

## Key facts

- **NIH application ID:** 10116374
- **Project number:** 5R01DK124420-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Gregory T Tietjen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $509,756
- **Award type:** 5
- **Project period:** 2020-02-28 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116374

## Citation

> US National Institutes of Health, RePORTER application 10116374, Mechanisms and Ex Vivo Repair of Cold-Storage Injury in Human Kidney Allografts (5R01DK124420-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10116374. Licensed CC0.

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