Current Status of the Measurement of Blood Hepcidin Levels in Chronic Kidney Disease

Abstract

Hepcidin is a small defensin-like peptide produced in the liver in response to anemia, hypoxia, or inflammation. In addition to its anti-microbial properties, it has also been found to be a key regulator of iron utilization, providing increased understanding of why chronic kidney disease patients absorb iron poorly from the gut and also why many hemodialysis patients develop functional iron deficiency in the presence of inflammation. Hepcidin synthesis is upregulated in uremia, as in other inflammatory states. The ability to measure hepcidin in biologic fluids has stimulated interest in the potential applicability of this measurement as a more informative marker of iron status than the traditional iron indices such as serum ferritin and transferrin saturation. Until recently, however, the assays for measuring hepcidin have lacked precision, accuracy, and internal validation. Over the last few years, however, several assays have become available that address these limitations. Broadly speaking, these can be divided into radioimmunoassays, ELISAs, and mass spectrometry methods. The purpose of this review is to outline the various assays available at the present time, to critique their advantages and limitations, and to report comparative data in patients with chronic kidney disease. A concern with the immunoassays is that they detect more than biologically active hepcidin-25. Mass spectrometric assays are specific for hepcidin-25 but are labor intensive and require more costly and sophisticated instrumentation. Thus, although mass spectrometry is more accurate, it is less practical for routine clinical use at the present time.

Urinary Hepcidin-25 and Risk of Acute Kidney Injury Following Cardiopulmonary Bypass

“…Second, there is no standardization for quantification of the differences between immunoassays and mass spectrophotometric assays (30). A recent international study was done with the goal of harmonizing hepcidin-25 measurement, and it demonstrated up to a tenfold difference between assays (31).…”

Hepcidin as a new biomarker for detecting autologous blood transfusion

“…However, the impact of blood reinfusion on hepcidin concentration is poorly understood. This paucity of information could be due to the difficulties faced when measuring hepcidin in blood samples via the standard immunological method [16,17]. Mass spectrometry may be a better way to measure hepcidin in the compared to immunological methods blood [17,18].…”

Hepcidin testing; establishing reference values for the Namibian blood donor population

“…In their review, Macdougall et al [15] discussed the different methodologies available for Hepcidin testing including the ELISA technique. In their review, a number of studies done on Hepcidin using the ELISA technique were discussed.…”

“…In Macdougall et al review [15], it appears Koliakari et al used wells coated with polyclonal antibodies whereas in Ganz's work the wells were coated with monoclonal antibodies against hepcidin. They noted that Koliaraki et al as well as Ganz et al work on ELISA conferred that there is no cross reactivity between the hepcidin isoforms when using the ELISA technique [15]. An ELISA based immunoassay was chosen because its performance is comparable to other technologies.…”