Can ionized calcium-estimating equations replace albumin-corrected calcium?-a narrative review

Background and Objective: An accurate appraisal of ionized calcium status is important for clinical management and prognosis in many domains of medicine, such as critical care and renal disease. The direct measurement of ionized calcium is still relatively costly and not entirely routine, especially in low -resource areas, but the popular indirect method, which infers ionized calcium status from the value of total calcium (TCa) corrected for albumin, has fared poorly in validation studies. There is a need for a validated indirect method of screening for patients at risk of abnormal ionized calcium based on routine data to serve as a guide for direct testing. The aim of this article is to review some of the newer models that estimate ionized calcium from additional routinely obtained biochemical data besides TCa and albumin and that have undergone successful external validation. Methods: Literature in English reporting or validating models of either albumin -corrected calcium or ionized calcium from 1935 to 14 February 2022 were retrieved from PubMed and Google Scholar using these search terms: corrected calcium; adjusted calcium; calcium equation; ionized calcium; hypocalcemia; hypercalcemia. Validated models of ionized calcium status were identified and synthesized into a narrative overview. Key Content and Findings: We identified several recently published models of ionized calcium that were derived in cohorts of inpatients, critical care patients, or renal patients, and that showed better discrimination for ionized hypocalcemia and hypercalcemia compared with albumin -corrected calcium in validation studies. While these models continue to use TCa and albumin as inputs, they have in common the use of other independent variables drawn from routine data, such as phosphate or the components of the anion gap, that appear to further account for the complexation of calcium by small anions. Conclusions: New ionized calcium models have been derived that can help clinicians and laboratories better screen more seriously ill patients for ionized calcium testing. The generalizability of these models to less seriously ill patients merits further investigation.