Evaluation and Treatment of Iron Deficiency Anemia: A Gastroenterological Perspective

A substantial volume of the consultations requested of gastroenterologists are directed towards the evaluation of anemia. Since iron deficiency anemia often arises from bleeding gastrointestinal lesions, many of which are malignant, establishment of a firm diagnosis usually obligates an endoscopic evaluation. Although the laboratory tests used to make the diagnosis have not changed in many decades, their interpretation has, and this is possibly due to the availability of extensive testing in key populations. We provide data supporting the use of the serum ferritin as the sole useful measure of iron stores, setting the lower limit at 100 μg/l for some populations in order to increase the sensitivity of the test. Trends of the commonly obtained red cell indices, mean corpuscular volume, and the red cell distribution width can provide valuable diagnostic information. Once the diagnosis is established, upper and lower gastrointestinal endoscopy is usually indicated. Nevertheless, in many cases a gastrointestinal source is not found after routine evaluation. Additional studies, including repeat upper and lower endoscopy and often investigation of the small intestine may thus be required. Although oral iron is inexpensive and usually effective, there are many gastrointestinal conditions that warrant treatment of iron deficiency with intravenous iron

Hepcidin-25 in Chronic Hemodialysis Patients Is Related to Residual Kidney Function and Not to Treatment with Erythropoiesis Stimulating Agents

Hepcidin-25, the bioactive form of hepcidin, is a key regulator of iron homeostasis as it induces internalization and degradation of ferroportin, a cellular iron exporter on enterocytes, macrophages and hepatocytes. Hepcidin levels are increased in chronic hemodialysis (HD) patients, but as of yet, limited information on factors associated with hepcidin-25 in these patients is available. In the current cross-sectional study, potential patient-, laboratory- and treatment-related determinants of serum hepcidin-20 and -25, were assessed in a large cohort of stable, prevalent HD patients. Baseline data from 405 patients (62% male; age 63.7±13.9 [mean SD]) enrolled in the CONvective TRAnsport STudy (CONTRAST; NCT00205556) were studied. Predialysis hepcidin concentrations were measured centrally with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Patient-, laboratory- and treatment related characteristics were entered in a backward multivariable linear regression model. Hepcidin-25 levels were independently and positively associated with ferritin (p<0.001), hsCRP (p<0.001) and the presence of diabetes (p = 0.02) and inversely with the estimated glomerular filtration rate (p = 0.01), absolute reticulocyte count (p = 0.02) and soluble transferrin receptor (p<0.001). Men had lower hepcidin-25 levels as compared to women (p = 0.03). Hepcidin-25 was not associated with the maintenance dose of erythropoiesis stimulating agents (ESA) or iron therapy. In conclusion, in the currently studied cohort of chronic HD patients, hepcidin-25 was a marker for iron stores and erythropoiesis and was associated with inflammation. Furthermore, hepcidin-25 levels were influenced by residual kidney function. Hepcidin-25 did not reflect ESA or iron dose in chronic stable HD patients on maintenance therapy. These results suggest that hepcidin is involved in the pathophysiological pathway of renal anemia and iron availability in these patients, but challenges its function as a clinical parameter for ESA resistance

Iron Administration, Infection, and Anemia Management in CKD: Untangling the Effects of Intravenous Iron Therapy on Immunity and Infection Risk

Patients with chronic kidney disease (CKD) are at increased risk for infection, attributable to immune dysfunction, increased exposure to infectious agents, loss of cutaneous barriers, comorbid conditions, and treatment-related factors (eg, hemodialysis and immunosuppressant therapy). Because iron plays a vital role in pathogen reproduction and host immunity, it is biologically plausible that intravenous iron therapy and/or iron deficiency influence infection risk in CKD. Available data from preclinical experiments, observational studies, and randomized controlled trials are summarized to explore the interplay between intravenous iron and infection risk among patients with CKD, particularly those receiving maintenance hemodialysis. The current evidence base, including data from a recent randomized controlled trial, suggests that proactive judicious use of intravenous iron (in a manner that minimizes the accumulation of non–transferrin-bound iron) beneficially replaces iron stores while avoiding a clinically relevant effect on infection risk. In the absence of an urgent clinical need, intravenous iron therapy should be avoided in patients with active infection. Although serum ferritin concentration and transferrin saturation can help guide clinical decision making about intravenous iron therapy, definition of an optimal iron status and its precise determination in individual patients remain clinically challenging in CKD and warrant additional study