Iron Deficiency in Chronic Kidney Disease: Updates on Pathophysiology, Diagnosis, and Treatment

Abstract

Anemia is a complication that affects a majority of individuals with advanced CKD. Although relative deficiency of erythropoietin production is the major driver of anemia in CKD, iron deficiency stands out among the mechanisms contributing to the impaired erythropoiesis in the setting of reduced kidney function. Iron deficiency plays a significant role in anemia in CKD. This may be due to a true paucity of iron stores (absolute iron deficiency) or a relative (functional) deficiency which prevents the use of available iron stores. Several risk factors contribute to absolute and functional iron deficiency in CKD, including blood losses, impaired iron absorption, and chronic inflammation. The traditional biomarkers used for the diagnosis of iron-deficiency anemia (IDA) in patients with CKD have limitations, leading to persistent challenges in the detection and monitoring of IDA in these patients. Here, we review the pathophysiology and available diagnostic tests for IDA in CKD, we discuss the literature that has informed the current practice guidelines for the treatment of IDA in CKD, and we summarize the available oral and intravenous (IV) iron formulations for the treatment of IDA in CKD. Two important issues are addressed, including the potential risks of a more liberal approach to iron supplementation as well as the potential risks and benefits of IV versus oral iron supplementation in patients with CKD.

Preoperative Intravenous Iron and Erythropoietin to Treat Severe Anemia in Patient With Stage 4 Kidney Disease Before Oncologic Surgery: A Case Report

“…We chose a conservative target for a CKD patient of a Hg of 9 g/dL to not delay surgery more than was necessary, because the surgeons anticipated a low risk of major blood loss. 5 Our patient's age, chronic anemia, and lack of cardiovascular disease suggested this was acceptable. Blood transfusions appear to result in immunomodulation that may lead to an increase in cancer progression.…”

“…Due to elevated levels of hepcidin and blood loss from frequent dialysis and blood draws, more than half of patients with advanced CKD are estimated to have IDA. 5 In practice, there may be concerns surrounding the robustness in Hg increase within the short time period between the preoperative visit and surgery especially in patients with CKD and cancer due to erythropoietin deficiency and bone marrow suppression. We discuss a case where a patient with stage 4 CKD, severe anemia, endometrial cancer, and vaginal bleeding benefitted from preoperative IV iron and erythropoietin treatment.…”

Management of Anemia in Nondialysis Chronic Kidney Disease: Current Recommendations, Real-World Practice, and Patient Perspectives

“…Functional ID is characterized by restricted iron availability, commonly due to inflammatory conditions. Inflammation induces the release of hepcidin and therefore, reduces gastrointestinal iron absorption as well as higher mobilization of stores in the reticuloendothelial system (8).…”

<p>Iron in the General Population and Specificities in Older Adults: Metabolism, Causes and Consequences of Decrease or Overload, and Biological Assessment</p>

“…13,39,40 In addition, AID can result from malnutrition, vegetarian diets (which cause AID but a priori with no anemia), or vegan diets (which are believed to cause AID with anemia). 28,41,42 Blood donors are also exposed to AID, as are patients with kidney failure, 18,43 which is particularly common in OAs. It has been shown that moderate chronic renal failure is present in almost all patients aged 80 and older hospitalized in a geriatric unit.…”

“…44 In kidney failure, AID, due to excessive blood loss and an abnormality of iron reabsorption, worsens anemia secondary to a defect in the synthesis of erythropoietin. 43 Finally, chronic alcohol abuse may be complicated by AID. 28 It is imperative to keep in mind that OAs often develop AID for multiple and interrelated reasons.…”