How to diagnose iron deficiency in chronic disease: A review of current methods and potential marker for the outcome

Abstract

Iron deficiency (ID) is the most common nutritional disorder worldwide. It is often observed in patients with chronic diseases, such as heart failure (HF), chronic kidney disease (CKD), inflammatory bowel disease (IBD) and cancer. ID is associated with poor clinical outcome, including poor performance, reduced quality of life, as well as increased hospitalization and mortality. The aim of this review is to provide an overview about the role of ID in chronic diseases (HF, CKD, IBD, cancer) regarding their current definitions and clinical relevance; diagnostic accuracy of iron parameters in chronic inflammatory conditions and its potential as prognostic markers. Due to different definitions and guideline recommendations of ID, various laboratory parameters for ID diagnostic exist and there is no general consensus about the definition of ID and its treatment. Still, a general trend can be observed across all investigated indications of this review (HF, CKD, IBD, cancer) that serum ferritin and transferrin saturation (TSAT) are the two parameters mentioned most often and emphasized in all guidelines to define ID and guide treatment. The most commonly used threshold values for the diagnosis of ID are TSAT of < 20% and serum ferritin of < 100–300 µg/L. Noteworthy, both TSAT and particularly ferritin are frequently applied, but both may vary due to inflammatory conditions. Studies showed that TSAT is less affected by inflammatory processes and may therefore be more accurate and reliable than serum ferritin, particularly in conditions with elevated inflammatory state. A low iron status and particularly a low TSAT value was associated with a poor outcome in all investigated indications, with the strongest evidence in HF patients. Routine surveillance of iron status in these groups of patients with chronic conditions is advisable to detect ID early. Depending on the inflammatory state, TSAT < 20% may be the more accurate diagnostic marker of ID than ferritin. Moreover, TSAT may also be the more reliable estimate for the prognosis, particularly in HF.

Iron Metabolic Biomarkers and the Mortality Risk in the General Population: A Nationwide Population-Based Cohort Study

“…Previous guidelines have recommended the measurement of SF concentrations, and some proposed TSAT as an alternative or complementary to define ID, that is SF less than 100 g/mL or 100 to 299 ng/mL with TSAT less than 20% [ 3 ]. However, some recent studies have realized that TSAT is a reliable diagnostic maker for ID with high sensitivity and specificity and should be recommended in clinical practice and a novel definition of ID based on TSAT alone has been suggested [ 37 ]. In a pulmonary vascular disease study, researchers found that ID, defined by TSAT less than 21%, best identifies patients with worse functional status and adverse clinical outcomes [ 38 ].…”

“…Second, individuals with DM had lower levels of TSAT compared to those without DM, and the Q1 group of TSAT was associated with higher CVD mortality risk and lower cancer mortality risk. TSAT reflects the proportion of circulating iron in the context of iron requirements and is less affected by inflammatory processes [ 37 , 39 , 40 ], which means the ID was more pronounced in individuals with diabetes leading to cardiomyocyte energy metabolism disorders, and increased risk of CVD mortality. In addition to its role in the generation of ROS, iron may be a limiting nutrient to the growth and replication of cancer cells in the human body, which may be responsible for the lowest cancer mortality risk when iron is deficient [ 15 ].…”

Scrutinizing Clinical Biomarkers in a Large Cohort of Patients with Lyme Disease and Other Tick-Borne Infections

“…Studies have suggested iron deficiency could exist even with expected Hg results [ 73 ]. In such cases, low transferrin saturation and low ferritin levels could support a diagnosis of iron deficiency, especially if patients suffer from a chronic condition [ 73 , 74 , 75 ]. Iron is used by bacteria such as M. tuberculosis for growth and can even trigger HIV reactivation [ 76 ].…”

Iron deficiency in children with a focus on inflammatory conditions

“…Absolute ID can occur in cases of increased demand, decreased iron intake or absorption, or chronic blood loss ( Table 1 ). Absolute ID is characterized by low levels of stored iron, resulting in low serum ferritin and reduced transferrin levels [ 7 ].…”