Anemia coincident with hyporesponsiveness to
erythropoiesis-stimulating agents is an ongoing and prevalent problem in children with
chronic kidney disease (CKD). The recently identified
iron-regulatory protein hepcidin appears likely to play a significant role in this problem.
Hepcidin up-regulation in the setting of CKD, with subsequent increased serum levels, results in impaired
iron absorption from the intestine and decreased
iron release from body storage sites. Ultimately, in the setting of such elevated levels, a state of functional
iron deficiency may develop and lead to
anemia due to
iron-restricted erythropoiesis. Elevated
hepcidin levels are expected in the face of decreased glomerular filtration rate and
inflammation. Based on current evidence, it seems likely that
hepcidin represents a potentially modifiable mediator of
anemia of CKD and is thus a potential target for future
anemia therapy. Currently, increased removal via intensified dialysis and-/or blockade of the inflammatory pathway appear to be two viable generic strategies for reducing
hepcidin levels. Goals of directly manipulating the
hepcidin pathway should offer the pediatric clinician new options for treating the complex
anemia associated with CKD.