Serum iron protects from renal postischemic injury

Céline Vaugier, Mariane T. Amano, Jonathan M. Chemouny, Michael Dussiot, Claire Berrou, Marie Matignon, Sanae Ben Mkaddem, Pamella H.M. Wang, Aurélie Fricot, Thiago T. Maciel, Damien Grapton, Jacques R.R. Mathieu, Carole Beaumont, Marie Noélle Peraldi, Carole Peyssonnaux, Laurent Mesnard, Eric Daugas, François Vrtovsnik, Renato C. Monteiro, Olivier HermineYelena Z. Ginzburg, Marc Benhamou, Niels O.S. Camara, Martin Flamant, Ivan C. Moura

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Renal transplants remain amedical challenge, because the parameters governing allograft outcome are incompletely identified. Here, we investigated the role of serum iron in the sterile inflammation that follows kidney ischemia-reperfusion injury. In a retrospective cohort study of renal allograft recipients (n=169), increased baseline levels of serum ferritin reliably predicted a positive outcome for allografts, particularly in elderly patients. In mice, systemic iron overload protected against renal ischemia-reperfusion injury-associated sterile inflammation. Furthermore, chronic iron injection inmice prevented macrophage recruitment after inflammatory stimuli. Macrophages cultured in high-iron conditions had reduced responses to Toll-like receptor-2, -3, and -4 agonists, which associatedwith decreased reactive oxygen species production, increased nuclear localization of theNRF2 transcription factor, increased expression of the NRF2-related antioxidant response genes, and limited NF-kB and proinflammatory signaling. In macrophage-depleted animals, the infusion of macrophages cultured in highiron conditions did not reconstitute AKI after ischemia-reperfusion, whereas macrophages cultured in physiologic iron conditions did. These findings identify serum iron as a critical protective factor in renal allograft outcome. Increasing serum iron levels in patients may thus improve prognosis of renal transplants.

Original languageEnglish
Pages (from-to)3605-3615
Number of pages11
JournalJournal of the American Society of Nephrology : JASN
Volume28
Issue number12
DOIs
StatePublished - Dec 2017
Externally publishedYes

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