| First Author | Vaugier C | Year | 2017 |
| Journal | J Am Soc Nephrol | Volume | 28 |
| Issue | 12 | Pages | 3605-3615 |
| PubMed ID | 28784700 | Mgi Jnum | J:290402 |
| Mgi Id | MGI:6436202 | Doi | 10.1681/ASN.2016080926 |
| Citation | Vaugier C, et al. (2017) Serum Iron Protects from Renal Postischemic Injury. J Am Soc Nephrol 28(12):3605-3615 |
| abstractText | Renal transplants remain a medical 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 in mice 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 associated with decreased reactive oxygen species production, increased nuclear localization of the NRF2 transcription factor, increased expression of the NRF2-related antioxidant response genes, and limited NF-kappaB and proinflammatory signaling. In macrophage-depleted animals, the infusion of macrophages cultured in high-iron 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. |
