RESUMO
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-κB 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.
Assuntos
Ferro/sangue , Rim/patologia , Traumatismo por Reperfusão/prevenção & controle , Adulto , Aloenxertos , Animais , Antioxidantes/metabolismo , Feminino , Ferritinas/sangue , Taxa de Filtração Glomerular , Humanos , Inflamação , Ferro/química , Rim/metabolismo , Transplante de Rim , Macrófagos/citologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Monócitos/citologia , Fator 2 Relacionado a NF-E2/metabolismo , Peritonite/metabolismo , Prognóstico , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/metabolismo , Transdução de SinaisRESUMO
Acquired Fanconi syndrome can occur in patients with monoclonal gammopathy or after exposure to heavy metals or drug agents such as ifosfamide, and some antiretroviral therapies. Fanconi syndrome is characterized by a dysfunctional of the proximal tubular responsible in its complete form for polyuria, hypokalemia, glycosuria, hypophosphatemia and low molecular weight proteinuria. We report the case of a 22-year-old patient hospitalized with an acute renal failure secondary to a tubulo-interstitial nephritis associated with a complete Fanconi syndrome in a context of a poor general condition and fever. We described and analyzed the process leading to the diagnosis.
