ArticleNature communications2025
Normothermic human kidney preservation drives iron accumulation and ferroptosis.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Isolated perfusion of pig kidney segments to study renal function: a translational model for human kidneys.Laboratory animals · 2026Article
- An Ex Vivo Patient-Derived Tumor-Bearing Human Kidney Model Recapitulates Drug Toxicity and Metabolic Distribution.Research (Washington, D.C.) · 2026Article
- Opportunities and challenges with the implementation of normothermic machine perfusion in kidney transplantation.Nature communications · 2025Review
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Authors and funding
13 authors.
Funding
Abstract
Ex vivo normothermic machine perfusion has been proposed to protect deceased donor kidneys. However, its benefits remain ambiguous. We postulate that the use of red blood cells (RBCs) and associated secondary hemolysis may in fact cause renal injury, offsetting potential advantages. During 48-hour normothermic perfusion of seven human donor kidneys, we observed progressive hemolysis, leading to iron accumulation in perfusate and tissue. Untargeted lipidomic profiling revealed significant increases in oxidized phospholipid species in perfused kidneys, pointing towards iron-dependent cell death known as ferroptosis. Next, in twelve additional perfusions, we assessed strategies to mitigate hemolysis-driven injury. Dialysis-based free hemoglobin removal reduced lipid peroxidation, but a ferroptosis gene signature persisted. In contrast, cell-free perfusion at subnormothermia negated iron accumulation, the ferroptosis gene signature, phospholipid peroxidation, and acute kidney injury. Our findings highlight the pathological role of hemolysis and iron on the kidney, urging restraint in the clinical application of RBC-based kidney perfusion.
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