Use of Albumin-Adjusted Calcium Measurements in Clinical Practice

Importance: Using albumin-adjusted calcium is commonly recommended for for measuring calcium, but with little empirical evidence to support the practice. Objective: To assess the correlation between total calcium measurements (with or without adjustment) vs the ionized calcium level as a reference standard. Design, Setting, and Participants: This was a population-based cross-sectional study in the province of Alberta, Canada, including adults tested for serum total calcium and ionized calcium simultaneously between January 1, 2013, and October 31, 2019. Statistical analysis was performed from March 2023 to October 2024. Main Measures and Outcomes: The correlation between unadjusted and adjusted total calcium measurements (using 10 formulas) and the ionized calcium level was evaluated, along with the potential association with the classification of calcium status. Results: Among 22 658 patients included, 11 889 (52.5%) were female and 10 769 (47.5%) were male; the median (IQR) age was 60 (47-72) years. The unadjusted total calcium (R2 = 71.7%; 95% CI, 71.1%-72.2%) had a stronger correlation with ionized calcium than the commonly used simplified Payne formula (ie, total calcium mmol/L + 0.02 40 - albumin (g/L)) (R2 = 68.9%; 95% CI, 68.0%-69.6%) and correlated similarly to other formulas (Payne: lowest R2 = 60.3%; 95% CI, 59.3%-61.3%; and James: highest R2 = 76.7%; 95% CI, 76.1%-77.3%). When classifying patients into categories of hypocalcemia, normocalcemia, or hypercalcemia, unadjusted total calcium had the best overall agreement (74.5%) with ionized calcium compared with albumin-adjusted calcium using the original Payne and simplified Payne formulas (agreement 63.0% and 58.7%, respectively). Misclassification using the adjustment formulas was worse in the presence of hypoalbuminemia (albumin level <30 g/L). Conclusions and Relevance: In this cross-sectional study drawn from a contemporaneous population, there appeared to be heavy reliance on adjustment formulas for calcium in clinical practice with little gain but considerable risk of misclassification of true calcium status, especially in the presence of hypoalbuminemia. These results suggest that unadjusted total calcium was the best and most practical alternative to ionized calcium.