Evidence map›Paper›PMID 32627324›Full record

ArticleAmerican journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons2021

Lysis of cold-storage-induced microvascular obstructions for ex vivo revitalization of marginal human kidneys.

Jenna R DiRito, Sarah A Hosgood, Melanie Reschke, Claire Albert, Laura G Bracaglia, John R Ferdinand, Benjamin J Stewart, Christopher M Edwards, Anand G Vaish, Sathia Thiru and 7 more

Open access · greenAbstract read
In one paragraph

Article in American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
8.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Article
  5. Evaluation of the Prevalence of Occult Fibrin in Donor Organs, Its Origins, and Consequences: Insights From the COPE Studies.Transplant international : official journal of the European Society for Organ Transplantation · 2026
    Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Contrast-Enhanced Ultrasound to Assess Kidney Quality DuringTransplant international : official journal of the European Society for Organ Transplantation · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Rational nanoparticle design: Optimization using insights from experiments and mathematical models.Journal of controlled release : official journal of the Controlled Release Society · 2023
    Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. Honoring the gift: The transformative potential of transplant-declined human organs.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2023
    Article
  20. 48 h Normothermic Machine Perfusion With Urine Recirculation for Discarded Human Kidney Grafts.Transplant international : official journal of the European Society for Organ Transplantation · 2023
    Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors at 2 institutions in 2 countries.

Jenna R DiRitoDepartment of Surgery, University of Cambridge, Cambridge, UK.ORCID 0000-0002-8513-5937
Sarah A HosgoodDepartment of Surgery, University of Cambridge, Cambridge, UK.ORCID 0000-0002-8039-143X
Melanie ReschkeDepartment of Molecular Biophysics & Biochemistry, Yale University, New Haven, Connecticut, USA.
Claire AlbertDepartment of Biomedical Engineering, Yale University, New Haven, Connecticut, USA.
Laura G BracagliaDepartment of Biomedical Engineering, Yale University, New Haven, Connecticut, USA.
John R FerdinandMolecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.ORCID 0000-0003-0936-0128
Benjamin J StewartMolecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
Christopher M EdwardsDepartment of Surgery, Yale School of Medicine, New Haven, Connecticut, USA.
Anand G VaishDepartment of Surgery, Yale School of Medicine, New Haven, Connecticut, USA.
Sathia ThiruDepartment of Pathology, University of Cambridge, Cambridge, UK.
David C MulliganDepartment of Surgery, Yale School of Medicine, New Haven, Connecticut, USA.
Danielle J HaakinsonDepartment of Surgery, Yale School of Medicine, New Haven, Connecticut, USA.
Menna R ClatworthyMolecular Immunity Unit, Department of Medicine, University of Cambridge, Cambridge, UK.
W Mark SaltzmanDepartment of Biomedical Engineering, Yale University, New Haven, Connecticut, USA.
Jordan S PoberDepartment of Immunobiology, Yale University, New Haven, Connecticut, USA.
Michael L NicholsonDepartment of Surgery, University of Cambridge, Cambridge, UK.
Gregory T TietjenDepartment of Surgery, Yale School of Medicine, New Haven, Connecticut, USA.
Yale University · USUniversity of Cambridge · GB

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Yale Liver CenterP30DK034989 · NIDDK · YALE UNIVERSITY · PI YASUKO IWAKIRI · 1986 to 2026
$31.1M
PATHOPHYSIOLOGY OF ACUTE AND CHRONIC RENAL DISEASET32DK007276 · NIDDK · YALE UNIVERSITY · PI ARONSON, PETER S., CANTLEY, LLOYD G · 1986 to 2022
$9.3M
Mechanisms and Ex Vivo Repair of Cold-Storage Injury in Human Kidney AllograftsR01DK124420 · NIDDK · YALE UNIVERSITY · PI KULKARNI, SANJAY, POBER, JORDAN S · 2020 to 2024
$2.5M
Ex Vivo Nanoparticle Drug Delivery Targeted to Human Renal Allograft EndotheliumU01AI132895 · NIAID · YALE UNIVERSITY · PI POBER, JORDAN S, SALTZMAN, W. MARK · 2017 to 2021
$2.2M
Department of Health RP-2017-08-ST2-002NCATS NIH HHS UL1 TR001863NIAID NIH HHS U01 AI132895NIDDK NIH HHS P30 DK034989NIDDK NIH HHS R01 DK124420
6 · The paper itself

Abstract

Thousands of kidneys from higher-risk donors are discarded annually because of the increased likelihood of complications posttransplant. Given the severe organ shortage, there is a critical need to improve utilization of these organs. To this end, normothermic machine perfusion (NMP) has emerged as a platform for ex vivo assessment and potential repair of marginal organs. In a recent study of 8 transplant-declined human kidneys on NMP, we discovered microvascular obstructions that impaired microvascular blood flow. However, the nature and physiologic impact of these lesions were unknown. Here, in a study of 39 human kidneys, we have identified that prolonged cold storage of human kidneys induces accumulation of fibrinogen within tubular epithelium. Restoration of normoxic conditions-either ex vivo during NMP or in vivo following transplant-triggered intravascular release of fibrinogen correlating with red blood cell aggregation and microvascular plugging. Combined delivery of plasminogen and tissue plasminogen activator during NMP lysed the plugs leading to a significant reduction in markers of renal injury, improvement in indicators of renal function, and improved delivery of vascular-targeted nanoparticles. Our study suggests a new mechanism of cold storage injury in marginal organs and provides a simple treatment with immediate translational potential.

Indexed as

Kidney TransplantationOrgan PreservationHumansKidneyPerfusionTissue Plasminogen ActivatorTissue Plasminogen Activatorbasic (laboratory) research/sciencecoagulation and hemostasisdisease pathogenesiskidney biologykidney transplantation/nephrologythrombolytic therapy/thrombolysistranslational research/sciencevascular biology

Identifiers

PMID32627324
PMCPMC7775334
OpenAlexW3039670148

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.