Trial reportFrontiers in immunology2022
The Effects of Free Heme on Functional and Molecular Changes During
Trial report in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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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.
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.
Who cites it
10 citing papers in PubMed, 20 citations in OpenAlex.
- Comparison of Normothermic and Subnormothermic Machine Perfusion of Porcine Kidneys Using a Novel Fully Synthetic Perfusion Solution: A Proof-of-Concept Study.Journal of clinical medicine · 2026Article
- Cellular and Molecular Changes Induced by Various Preservation Temperatures and Methods of Preservation in Renal Grafts and Other Solid Organ Grafts.International journal of molecular sciences · 2026Review
- Improving outcomes in kidney transplantation through advances in donor organ perfusion.Nature reviews. Nephrology · 2025Review
- Regulated cell death and DAMPs as biomarkers and therapeutic targets in normothermic perfusion of transplant organs. Part 2: implementation strategies.Frontiers in transplantation · 2025Review
- Current Evidence and Future Perspectives to Implement Continuous and End-Ischemic Use of Normothermic and Oxygenated Hypothermic Machine Perfusion in Clinical Practice.Journal of clinical medicine · 2023Review
- How to Best Protect Kidneys for Transplantation-Mechanistic Target.Journal of clinical medicine · 2023Review
- Article
- Oxygen carriers affect kidney immunogenicity duringFrontiers in transplantation · 2023Article
- Pushing the boundaries of innovation: the potential ofFrontiers in cardiovascular medicine · 2023Review
- Differential Cytokine Levels during Normothermic Kidney Perfusion with Whole Blood- or Red Blood Cell-Based Perfusates-Results of a Scoping Review and Experimental Study.Journal of clinical medicine · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Normothermic machine perfusion (NMP) is a technique of kidney preservation designed to restore cellular metabolism after cold ischemia. Kidneys are perfused with an oxygenated banked red blood cell (RBC) based solution for 1h at 36°C. During NMP, RBCs can become damaged, releasing free heme into the perfusate. This can act as a damage-associated molecular pattern (DAMP) activating inflammatory signalling pathways. The aim of this study was to measure the levels of free heme during NMP, assess the effect on kidney function and determine any association with inflammatory and stress related gene expression. Levels of free heme were measured in perfusate samples from a series of donation after circulatory death (DCD) kidneys undergoing NMP as part of a randomised controlled trial (RCT). The age of RBCs and levels of free heme were correlated with perfusion parameters. Changes in gene expression were analysed in a series of kidneys declined for transplantation using the NanoString nCounter Organ Transplant Panel and qRT-PCR. Older units of RBCs were associated with higher levels of free heme and levels increased significantly during NMP (Pre 8.56 ± 7.19µM vs 26.29 ± 15.18µM, P<0.0001). There was no association with levels of free heme and perfusion parameters during NMP (P > 0.05). Transcriptional and qPCR analysis demonstrated the upregulation of differentially expressed genes associated with apoptosis (FOS and JUN), inflammatory cytokines (IL-6, SOCS3, ATF3), chemokines (CXCL8, CXCL2, CC3/L1) and oxidative stress (KLF4) after NMP. However, these did not correlate with levels of free heme (P >0.05). A significant amount of free heme can be detected in the perfusate before and after NMP particularly when older units of red cells are used. Although transcriptional analysis demonstrated significant upregulation of genes involved with apoptotic, inflammatory and oxidative pathways these were not associated with high levels of free heme.
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Registered trials
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.