Iron Balance in Chronic Kidney Disease

The review by Gattermann et al. (1), in my opinion, should discuss in more detail the insufficient supply of iron, as well as the complex connection between iron deficiency and erythropoietin, in chronic renal insufficiency or renal anemia, especially regarding the fact that about three-quarters of patients with a glomerular filtration rate of less than 15 mL/min have an absolute or functional iron deficiency. This is considered relevant for the morbidity and mortality risks of this patient group, independently of other factors.

The traditional biomarkers for assessing iron status are often unreliable in renal failure, both in terms of diagnostic and therapeutic procedures (2).

The restricted enteral iron absorption, or the reduced release from the body stores, is due to the severe impairment of the function of the hepcidin–ferroportin axis (2). Hepcidin is primarily upregulated in patients requiring dialysis. The restricted elimination and chronic inflammation play an important role. An increase in iron levels through parenteral administration, which is often practiced, can promote hepcidin production through binding to the transferrin receptor (TRF2) and reduce responsiveness to erythropoietin. Erythroferron induced by exogenous administration of erythropoietin appears to be attenuated in its inhibitory effect on hepcidin production (2).

Both hemodialysis and peritoneal dialysis can reduce the hepcidin concentration. The correlation between hepcidin and ferritin also persists in patients with kidney disease, but there is no connection between hepcidin and responsiveness to iron in patients not requiring dialysis (3).