Comparison of two ferritin assay platforms to assess their level of agreement in measuring serum and plasma ferritin levels in patients with chronic kidney disease

Abstract

Background Ferritin levels are used to make decisions on therapy of iron deficiency in patients with chronic kidney disease (CKD). Hyperferritinaemia, common among patients with CKD from the Northern Territory (NT) of Australia, makes use of ferritin levels as per clinical guidelines challenging. No gold standard assay exists for measuring ferritin levels. Significant variability between results from different assays creates challenges for clinical decision-making regarding iron therapy. In the NT, different laboratories use different methods. In 2018, Territory Pathology changed the assay from Abbott ARCHITECT i1000 (AA) to Ortho-Clinical Diagnostics Vitros 7600 (OCD). This was during the planning of the INtravenous iron polymaltose for First Nations Australian patients with high FERRitin levels on haemodialysis (INFERR) clinical trial. The trial design was based on AA assay ferritin levels. We compared the two assays’ level of agreement in measuring ferritin levels in CKD patients. Methods Samples from INFERR clinical trial participants were analysed. Other samples from patients whose testing were completed the same day on OCD analyzers and run within 24 h on AA analyzers were added to ensure wide range of ferritin levels, adding statistical strength to the comparison. Ferritin levels from both assays were compared using Pearson’s correlation, Bland–Altman, Deming and Passing-Bablok regression analyses. Differences between sample types, plasma and serum were assessed. Results Sixty-eight and 111 (179) samples from different patients from Central Australia and Top End of Australia, respectively, were analyzed separately and in combination. The ferritin levels ranged from 3.1 µg/L to 3354 µg/L and 3 µg/L to 2170 µg/L for AA and OCD assays respectively. Using Bland–Altman, Deming and Passing-Bablok regression methods for comparison, ferritin results were consistently 36% to 44% higher with AA than OCD assays. The bias was up to 49%. AA ferritin results were the same in serum and plasma. However, OCD ferritin results were 5% higher in serum than plasma. Conclusions When making clinical decisions, using ferritin results from the same assay in patients with CKD is critical. If the assay is changed, it is essential to assess agreement between results from the new and old assays. Further studies to harmonize ferritin assays are required.

Ferritin: A Biomarker Requiring Caution in Clinical Decision

“…This means that it is important for the clinical management of a patient that the analyses are carried out in the same laboratory. A similar conclusion was reached by researchers studying ferritin values among patients with chronic kidney disease [29]. Indeed, in this study, 179 blood samples were analyzed for ferritin using two different assays, with an observed bias of up to 49%.…”

“…The present data confirm previous studies, such as those of Birgegård in 1980, which compared samples from nine subjects, or more recently, those of Snozek et al in 2021, which compared serum and heparinized plasma, in which a correlation of 0.9992 was retrieved between these two matrices [27,28]. In their 2023 study, Majoni et al observed identical results using the chemiluminescent microparticle immunoassay (CMIA) method, but an overestimation of 5% with serum compared to heparinized plasma matrix using a two-phase immunometric method [29].…”

“…Our data are therefore far from those used to manage hemochromatosis. It would also be useful to study these analytical differences in a population of iron-deficient patients with renal diseases or inflammation [29].…”