ArticleJournal of the American Society of Nephrology : JASN2016
Renal Handling of Circulating and Renal-Synthesized Hepcidin and Its Protective Effects against Hemoglobin-Mediated Kidney Injury.
Article in Journal of the American Society of Nephrology : JASN, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Iron metabolism-related indicators as predictors of the incidence of acute kidney injury after cardiac surgery: a meta-analysis.Renal failure · 2023Pooled it
- Vamifeport, a clinical stage oral ferroportin inhibitor, alleviates murine lupus nephritis: A pilot study.Clinical immunology (Orlando, Fla.) · 2026Article
- Iron Biology in Acute Kidney Injury: Catalytic Iron, Hepcidin-Ferroportin Axis, and NGAL-A Narrative Review.International journal of molecular sciences · 2026Review
- Acute kidney injury and iron metabolism: A narrative review focusing on pathophysiology and therapy.Smart molecules : open access · 2025Review
- Article
- Iron as an emerging therapeutic target in critically ill patients.Critical care (London, England) · 2023Review
- Iron metabolism and chronic inflammation in IgA nephropathy.Renal failure · 2023Review
- HMGB1 induces hepcidin upregulation in astrocytes and causes an acute iron surge and subsequent ferroptosis in the postischemic brain.Experimental & molecular medicine · 2023Article
- Ferroptotic mechanisms and therapeutic targeting of iron metabolism and lipid peroxidation in the kidney.Nature reviews. Nephrology · 2023Review
- Distinctive modulation of hepcidin in cancer and its therapeutic relevance.Frontiers in oncology · 2023Review
- Renal hypoxia-HIF-PHD-EPO signaling in transition metal nephrotoxicity: friend or foe?Archives of toxicology · 2022Review
- Erythropoiesis-independent effects of iron in chronic kidney disease.Pediatric nephrology (Berlin, Germany) · 2022Article
- NGAL/hepcidin-25 ratio and AKI subtypes in patients following cardiac surgery: a prospective observational study.Journal of nephrology · 2022Observational
- Investigating the Molecular Mechanisms of Renal Hepcidin Induction and Protection upon Hemoglobin-Induced Acute Kidney Injury.International journal of molecular sciences · 2022Article
- Iron-Deficiency in Atopic Diseases: Innate Immune Priming by Allergens and Siderophores.Frontiers in allergy · 2022Review
- The Macrophage Iron Signature in Health and Disease.International journal of molecular sciences · 2021Review
- Role of hepcidin in oxidative stress and cell death of cultured mouse renal collecting duct cells: protection against iron and sensitization to cadmium.Archives of toxicology · 2021Article
- Heme Burden and Ensuing Mechanisms That Protect the Kidney: Insights from Bench and Bedside.International journal of molecular sciences · 2021Review
- Predictive Value of Plasma NGAL:Hepcidin-25 for Major Adverse Kidney Events After Cardiac Surgery with Cardiopulmonary Bypass: A Pilot Study.Annals of laboratory medicine · 2021Article
- Iron Metabolism: An Under Investigated Driver of Renal Pathology in Lupus Nephritis.Frontiers in medicine · 2021Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Urinary hepcidin may have protective effects against AKI. However, renal handling and the potential protective mechanisms of hepcidin are not fully understood. By measuring hepcidin levels in plasma and urine using mass spectrometry and the kidney using immunohistochemistry after intraperitoneal administration of human hepcidin-25 (hhep25) in C57Bl/6N mice, we showed that circulating hepcidin is filtered by the glomerulus and degraded to smaller isoforms detected in urine but not plasma. Moreover, hepcidin colocalized with the endocytic receptor megalin in proximal tubules, and compared with wild-type mice, megalin-deficient mice showed higher urinary excretion of injected hhep25 and no hepcidin staining in proximal tubules that lack megalin. This indicates that hepcidin is reaborbed in the proximal tubules by megalin dependent endocytosis. Administration of hhep25 concomitant with or 4 hours after a single intravenous dose of hemoglobin abolished hemoglobin-induced upregulation of urinary kidney injury markers (NGAL and KIM-1) and renal Interleukin-6 and Ngal mRNA observed 24 hours after administration but did not affect renal ferroportin expression at this point. Notably, coadministration of hhep25 and hemoglobin but not administration of either alone greatly increased renal mRNA expression of hepcidin-encoding Hamp1 and hepcidin staining in distal tubules. These findings suggest a role for locally synthesized hepcidin in renal protection. Our observations did not support a role for ferroportin in hhep25-mediated protection against hemoglobin-induced early injury, but other mechanisms of cellular iron handling may be involved. In conclusion, our data suggest that both systemically delivered and locally produced hepcidin protect against hemoglobin-induced AKI.
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Registered trials
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