Clinical question: Is albumin-adjusted calcium a reliable surrogate for determining true calcium status, particularly when compared to ionized calcium, in adult patients?
Background: Albumin-adjusted calcium is widely used in clinical practice to estimate true calcium status, despite limited empirical evidence supporting its accuracy. Ionized calcium is the physiologically active form and the gold standard for assessing calcium status, but it is measured less frequently due to issues of cost, convenience, and limited availability in certain clinical settings.
Study design: Retrospective cross-sectional study
Setting: Tertiary hospitals across Alberta, Canada
Synopsis: This population-based cross-sectional study included 22,658 adults (median age 60 years, 52.5% female) who underwent simultaneous measurement of serum total calcium, albumin, and ionized calcium between 2013 and 2019. The study compared the correlation and agreement of unadjusted total calcium and albumin-adjusted calcium (using 10 formulas, including Payne and James) with ionized calcium, the reference standard. The greatest discrepancies between albumin-adjusted and ionized calcium were observed in patients with hypoalbuminemia (albumin under 30 g/L), where adjustment formulas led to increased discordance and frequent misclassification of true hypocalcemia as normocalcemia, and less commonly normocalcemia as hypercalcemia. Using the original Payne formula, patients were misclassified by one category in 40.0% of cases and by two categories in 1.3% of cases, compared to 25.3% and 0.1%, respectively, for unadjusted total calcium. The James formula showed slightly better correlation, but no adjustment formula outperformed unadjusted total calcium, especially in low albumin states. Overall, unadjusted total calcium had a stronger correlation (R²=71.7%) and higher agreement (74.5%) with ionized calcium. Limitations included retrospective design, lack of clinical outcome data, and single-geographic scope.
Bottom line: Albumin-adjusted calcium often misclassifies clinically significant disturbances, supporting a shift toward using unadjusted total calcium or direct ionized calcium, particularly in patients with low albumin.
Citation: Desgagnés N, et al. Use of albumin-adjusted calcium measurements in clinical practice. JAMA Netw Open. 2025;8(1):e2455251. doi:10.1001/jamanetworkopen.2024.55251.
Dr. Parker is an oncology hospitalist at Smilow Cancer Hospital at Yale New Haven and an assistant clinical professor of medicine at Yale School of Medicine, both in New Haven, Conn