|Structure of hepcidin|
Source: Tomas Ganz, Blood, 2003
The main points made by Nancy Andrews excerpted from the article are:
"Ferroportin is a transmembrane iron exporter that transfers iron out of cells. This protein is important in the intestinal epithelium, where it allows dietary iron that is taken up by absorptive cells to enter the circulation, and in macrophages that recycle used iron from effete red cells.
Hepcidin, a small peptide produced by the liver, controls the activity of ferroportin by attaching to it and targeting the protein for destruction in the lysosome. Hepcidin levels fluctuate in response to the body's iron needs. In simple terms, more hepcidin causes less iron absorption, and less hepcidin causes more iron absorption."
|Normal Iron Balance|
I would also highly recommend a mini-review by Dan Coyne, published in Kidney International that is available open access.
The main points from Dan Coyne’s article are:
|Source: HDCN (ANNA Symposium, 2005)|
2. Elevated hepcidin contributes to the dysregulation of iron homeostasis in CKD.
3. In patients with CKD, although parenteral iron in CKD can bypass some of the iron-blocking effects of hepcidin, free iron and iron stores increase, anemia is only partially corrected, and ESA dose requirements remain significantly higher than physiological replacement.
Key facts about hepcidin from Dan Coyne’s article are:
1. Hepcidin controls intestinal absorption of iron and its distribution throughout the body.
2. The liver produces hepcidin.
|Iron deficiency in CKD|
4. The kidney is the major route of hepcidin clearance.
5. Hepcidin, prohepcidin, and hepcidin metabolites increase in chronic kidney disease (CKD) and are very high in dialysis patients.
6. Elevated hepcidin appears to have a major role in the development and severity of anemia in CKD.
The bottom-line: we are in for an interesting few years in the management of CKD anemia. Not only do we have exciting new ESAs emerging onto the clinical stage, but also the world of new iron therapies is not far behind.