Markers of iron status in chronic kidney disease

Abstract

Anemia is one of the main comorbidities related to Chronic Kidney Disease (CKD). Until the advent of Erythropoiesis Stimulating Agents (ESA), endogenous erythropoietin deficiency has been thought to be the main culprit of anemia in CKD patients. The use of ESA’s has shed new light on the physiology of CKD anemia, where iron homeostasis plays an increasingly important role. Disorders of iron homeostasis occurring in CKD turn the anemia management in those patients into a complex multifactorial therapeutic task, where ESA and Iron dose must be properly balanced to achieve the desired outcome without exposing the patients to the risk of serious adverse events. This review covers diagnostic markers traditionally used for quantifying iron status in CKD patients, such as serum ferritin and transferrin saturation, new ones, such as reticulocyte hemoglobin content and percent hypochromic red cells, as well as experimental ones, such as hepcidin and soluble transferrin receptor. Each marker is presented in terms of their diagnostic performance, followed by biological and analytical variability data. Advantages and disadvantages of each marker are briefly discussed. Although serum ferritin and transferrin saturation are easily available, they exhibit large biological variability and require caution when used for diagnosing iron status in CKD patients. Reticulocyte hemoglobin content and the percentage of hypochromic red cells are more powerful, but their widespread use is hampered by the issue of sample stability in storage. Soluble transferrin receptor and hepcidin show promise, but require further investigation as well as the development of standardized, low-cost assay platforms.

Using transferrin saturation as a diagnostic criterion for iron deficiency: A systematic review

“…The diagnosis of ID was addressed in some publications (n=36) in the general population 3,[8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] or specific conditions including pregnancy 25 , older subjects 5 , chronic diseases 4 , IBD 2,26-29 , CKD [30][31][32][33][34][35][36] , and CHF 7,37,38 . Other publications (n=5) focused on the levels of one of the markers of ID, either serum ferritin [39][40][41] or transferrin 42,43 .…”

Impact of Inflammation on Ferritin, Hepcidin and the Management of Iron Deficiency Anemia in Chronic Kidney Disease

“…As negative acute phase reactants, concentrations of serum iron and Tf, an iron transport protein, are decreased in response to inflammation [ 14 , 41 , 42 , 43 ]. Low TSAT (<20%) with low serum ferritin is diagnostic of IDA [ 1 , 44 ]. Low TSAT combined with normal or elevated serum ferritin is diagnostic of FIDA [ 44 ].…”

“…Low TSAT (<20%) with low serum ferritin is diagnostic of IDA [ 1 , 44 ]. Low TSAT combined with normal or elevated serum ferritin is diagnostic of FIDA [ 44 ]. As discussed later, many international guidelines for the management of IDA in CKD use the combination of low serum ferritin and TSAT for diagnosis of IDA.…”

“…As discussed later, many international guidelines for the management of IDA in CKD use the combination of low serum ferritin and TSAT for diagnosis of IDA. TSAT represents the percentage of binding sites on all Tf molecules occupied with iron molecules and is calculated as the ratio of serum iron to Tf or serum iron to total iron-binding capacity (TIBC) which indicates the maximum amount of iron necessary to saturate all available transferrin iron-binding sites [ 1 , 44 ]. TIBC is a negative acute-phase reactant and reduction in TIBC induced by inflammation leads to higher TSAT levels independent of iron status [ 41 ].…”

“…Thus, reliability of TSAT as a measure of iron status is reduced by inflammation associated with CKD. Soluble TfR (sTfR), which is produced by proteolysis of the membrane TfR, is increased in HD patients with ID and inversely correlated with the amount of iron available for erythropoiesis [ 44 ]. As a marker of iron status, sTfR is not an acute-phase reactant and less influenced by inflammation than serum ferritin is, while it is increased in individuals with general inflammation [ 14 ].…”