Iron and Chronic Kidney Disease: Still a Challenge

Abstract

Anemia is a clinical feature of chronic kidney disease (CKD). Most common causes are iron and erythropoietin deficiency. The last two decades have yielded significant advances in understanding iron balance's physiology, including iron trafficking and the crosstalk between iron, oxygen, and erythropoiesis. This knowledge sheds new light on the regulation and disturbance of iron homeostasis in CKD and holds the promise for developing new diagnostic and therapeutic tools to improve the management of iron disorders. Hepcidin–ferroportin axis has a central role in regulating body iron balance and coordinating communication between tissues and cells that acquire, store, and utilize iron. Recent research has revealed a bidirectional relationship between fibroblast growth factor 23 (FGF23) and iron status, anemia, and inflammation, as well as the role of erythroferrone (ERFE) in iron homeostasis. However, ERFE concentrations and actions are not well-characterized in CKD patients. Studies on ERFE in CKD are limited with slightly conflicting results. Despite general interest in iron metabolism in kidney diseases, studies on the less prevalent renal replacement therapy mode, such as peritoneal dialysis or hemodiafiltration, are scarce. Slightly more was published on hemodialysis. There are several novel options on the horizon; however, clinical data are limited. One should be aware of the potential risks and benefits of the novel, sophisticated therapies. An inhibition of hepcidin on the different pathways might be also a viable adjunctive therapeutic option in other clinical situations.

Serum Hepcidin-25 and All-Cause Mortality in Patients Undergoing Maintenance Hemodialysis

“…10 Therefore, hepcidin-25 could be a supplement for evaluating functional iron deficiency to conventional iron indices in patients receiving MHD. 22 KNOW-CKD study 23 demonstrated that high hepcidin-25 was associated with anemia in patients with non-dialysis CKD. Serum hepcidin was positively correlated with ferritin but had no relationship with inflammatory cytokines and TSAT.…”

“… 10 Therefore, hepcidin-25 could be a supplement for evaluating functional iron deficiency to conventional iron indices in patients receiving MHD. 22 …”

Ironing out mechanisms of iron homeostasis and disorders of iron deficiency

“…Chronic kidney disease Normocytic anemia is a common finding among chronic kidney disease (CKD) patients, mainly due to elevated hepcidin (and reduced iron availability) and decreased EPO levels (98). Increased production of hepcidin is likely secondary to chronic inflammation and decreased renal clearance of this peptide (99). As a result of decreased renal production of EPO, CKD patients generally need erythropoiesis-stimulating agents (ESAs) (99).…”

Current Status of Renal Anemia Pharmacotherapy—What Can We Offer Today

“…Furthermore, ferric citrate has been proven effective in reducing iv iron and ESA needs, with a good tolerability, in patients undergoing HD [ 131 ]. The liposomal iron represents another example of a new generation of oral iron preparations, which shows high gastrointestinal absorption and high bioavailability [ 132 ]. Compared with other traditional oral iron agents, liposomal iron avoids the direct contact of iron with the intestinal mucosa and bypasses the intestinal hepcidin–ferroportin block via a different uptake mechanism.…”