Iron-Deficiency Anemia in CKD: A Narrative Review for the Kidney Care Team

Abstract

Anemia is a common complication of chronic kidney disease (CKD) and is associated with increased mortality and reduced health-related quality of life. Anemia is characterized by a decrease in hemoglobin, the iron-rich protein that the body uses for oxygen transport. Iron is required to produce hemoglobin, and disruptions in the iron homeostasis can lead to iron-deficiency anemia. Management of anemia in individuals with CKD is typically performed by a team of physicians, nurse practitioners, physician assistants, or registered nurses. Throughout the care continuum, the management can be enhanced by multidisciplinary care, and individuals with CKD can benefit from the involvement of other specialties, with dietitians/nutritionists playing an important role. However, a key area of unmet clinical need is how to assess and address iron-deficiency anemia. This review aims to provide an overview of iron-deficiency anemia in CKD and how this may be diagnosed and managed by the entire kidney care team, such as describing the mechanisms underlying iron homeostasis, the complications of iron-deficiency anemia, and the current challenges associated with its diagnosis and treatment in CKD. Opportunities for each multidisciplinary team member to add value to the care of individuals with CKD and iron-deficiency anemia are also described.

Keywords: Anemia; chronic kidney disease; hemoglobin; iron deficiency; iron metabolism; iron-deficiency anemia.

Figure 1

Overview of normal iron homeostasis. Iron is a key component of hemoglobin, which is used by RBCs to transport oxygen. Approximately 24 mg of iron per day is necessary for RBC production. Dietary iron is absorbed by the enterocyte; ∼1 to 2 mg must be replaced through gastrointestinal absorption per day. Iron binds to transferrin (an iron transport protein) in the blood. Transferrin delivers iron to the bone marrow (site of hemoglobin formation and RBC production). Iron not found in the circulation is largely stored in the liver and spleen bound to ferritin (an iron-storage protein). Iron is largely recycled from aged RBCs (∼120 days old), which are degraded by macrophages. Transferrin also binds to and transports the iron released from macrophages. EPO, erythropoietin; GI, gastrointestinal; RBC, red blood cells.

Figure 2

Hepcidin regulates iron absorption and iron availability. Hepcidin production is stimulated in the liver in response to increased iron uptake, inflammation, and infection (step 1); high levels of hepcidin result in limited iron availability because iron is sequestered by the intestine and macrophages (step 2) ferroportin serves as an exporter of iron into circulation. Because of high levels of hepcidin, ferroportin interacts with hepcidin, which results in endocytosis and degradation. The degradation of ferroportin leads to impaired iron absorption and release from the iron-storage sites, which results in decreased red blood cell production (step 3).

Figure 3

Functional versus absolute iron deficiency.^,, Depending on its cause, iron deficiency can be categorized as absolute or functional. Both forms of iron deficiency are common in CKD. CKD, chronic kidney disease; ESA, erythropoietin-stimulating agent; GI, gastrointestinal; TSAT, transferrin saturation.

Figure 4

Prescriptions for anemia management in US individuals with NDD-CKD with hemoglobin concentration of <11.0 g/dL. CKD, chronic kidney disease; ESA, erythropoietin-stimulating agent; IV, intravenous; NDD, non–dialysis-dependent.

Figure 5

A flow chart for the assessment, diagnosis, and management of iron-deficiency anemia in patients with CKD^,, ∗For individuals with NDD-CKD who have hemoglobin concentrations of <10.0 g/dL, KDIGO recommends that the decision to initiate ESA therapy be individualized based on the rate of decrease of the hemoglobin concentration, previous response to iron therapy, the risk of needing a transfusion, the risks related to ESA therapy, and the presence of symptoms attributable to anemia. For individuals with CKD, KDIGO suggests using ESA therapy to avoid hemoglobin concentration decreasing to <9.0 g/dL by initiating ESA therapy when hemoglobin concentration is 9.0-10.0 g/dL. ^†On the basis of individual symptoms and overall clinical goals such as avoidance of transfusion and improvement in anemia-related symptoms and after exclusion of active infection and other causes of ESA hyporesponsiveness. ^‡Benefits of iron therapy should be balanced with risks of harm in individuals (eg, anaphylactoid/other acute reactions and unknown long-term risks). ∗∗Disease settings of celiac disease, anemia of chronic disease, and autoimmune gastritis. CKD, chronic kidney disease; ESA, erythropoiesis-stimulating agent; IV, intravenous; KDIGO, Kidney Disease Improving Global Outcomes; NDD, non–dialysis-dependent; TSAT, transferrin saturation.