| Theme |
Problems to be solved in the therapy for renal anemia : Association of ESA hyporesponsiveness with dysregulated iron metabolism |
| Title |
Dysregulated iron metabolism in chronic kidney disease |
| Author |
Takeshi Nakanishi |
Division of Kidney and Dialysis, Department of Internal Medicine, Hyogo College of Medicine |
| Author |
Masayoshi Nanami |
Division of Kidney and Dialysis, Department of Internal Medicine, Hyogo College of Medicine |
| Author |
Yukiko Hasuike |
Division of Kidney and Dialysis, Department of Internal Medicine, Hyogo College of Medicine |
| [ Summary ] |
We hypothesize that dysregulation of iron metabolism may be associated with infectious diseases and cardiovascular events which are the leading causes of mortality in patients on maintenance hemodialysis (MHD). Iron transport between intracellular and extracelluar regions, inflammatory cytokines and hepcidin, which may decrease the expression of the iron export protein, ferroportin have all been demonstrated to increase in these patients. This may cause iron sequestration in various types of cells. Intracellular iron metabolism is due to the mitochondrial iron-binding protein, frataxin. It can act as an iron chaperone protein and reduce the formation of Fe-sulfur cluster proteins which are lowered in MHD patients. The downregulation of frataxin is linked to hypercytokinemia and oxidative stress. Iron transport protein in endosomes, Nramp1, which can export iron from phagosomes/lysosomes, is downregulated. The decrease in Nramp1 causes iron retention in phagosomes, facilitates growth of intracellular pathogens and also hampers the handling of iron directed to mitochondria. From these observations, we can presume that the misregulation of iron metabolism and the mislocalization of iron in the cells may cause varioius complications via oxidative stress in MHD patients. |