A contemporary review of the limitations of adjusted calcium in clinical practice.

Since the 1970s, albumin-adjusted calcium has been widely used to approximate ionised calcium concentrations, particularly in patients with abnormal serum albumin levels. This adjustment was introduced to mitigate misclassification of calcium status when direct measurement of ionised calcium (technically demanding and resource-intensive at that time) was unavailable. Despite its historical utility, emerging evidence has highlighted significant limitations. This review critically examines the validity and clinical utility of adjusted calcium, with a focus on specific populations such as the elderly, critically ill, and those with kidney disease, in whom albumin derangement is more common. Adjusted calcium assumes stable ionised calcium levels across varying albumin concentrations and overlooks key modifiers such as pH, phosphate, lactate, and between-assay variability. Multiple studies demonstrate that adjusted calcium does not outperform unadjusted total calcium and may misclassify calcium status, particularly in patients with hypoalbuminaemia and impaired kidney function. Further limitations include variability in albumin assays and the derivation of adjustment formulas from non-representative populations. Adjusted calcium offers limited diagnostic value and should not replace ionised calcium where accurate assessment is essential. A reflex testing strategy, using total calcium as a screening tool, followed by ionised calcium testing when indicated, may provide a more reliable and pragmatic approach. Laboratory professionals and clinicians should recognise the considerable analytical and clinical limitations of adjusted calcium and interpret results with caution.