Calcium state estimation by total calcium: the evidence to end the never-ending story

Abstract

BackgroundTotal blood calcium (TCa) is routinely used to diagnose and manage mineral and bone metabolism disorders. Numerous laboratories adjust TCa by albumin, though literature suggests there are some limits to this approach. Here we report a large retrospective study on agreement rate between ionized calcium (iCa) measurement and TCa or albumin-adjusted calcium measurements.MethodsWe retrospectively selected 5055 samples with simultaneous measurements of iCa, TCa, albumin and pH. We subgrouped our patients according to their estimated glomerular filtration rate (eGFR), albumin levels and pH. We analyzed each patient’s calcium state with iCa as reference to determine agreement rate with TCa and albumin-adjusted calcium using Payne, Clase, Jain and Ridefelt formulas.ResultsThe Payne formula performed poorly in patients with abnormal albumin, eGFR or pH levels. In patients with low albumin levels or blood pH disorders, Payne-adjusted calcium may overestimate the calcium state in up to 80% of cases. Similarly, TCa has better agreement with iCa in the case of hypoalbuminemia, but performed similarly to the Payne formula in patients with physiological albumin levels. The global agreement rate for Clase, Jain and Ridefelt formulas suggests significant improvement compared to Payne calcium adjustment but no significant improvement compared to TCa.ConclusionsTotal and albumin-adjusted calcium measurement leads to a misclassification of calcium status. Moreover, accurate calcium state determination depends on blood pH levels, whose measurement requires the same pre-analytical restrictions as iCa measurement. We propose that iCa should instead become the reference method to determine the real calcium state.

The Prognostic Value of Calcium in Post-Cardiovascular Surgery Patients in the Intensive Care Unit

“…Although correction formulas have been used to adjust tCa with albumin level, their predicting capacity is diminished by various factors (7). Unlike tCa, iCa is unaffected by altered acid-base status or albumin level, thus making it a more reliable parameter in the assessment of patients' calcium status (8) and health status.…”

Serum ionised calcium and the risk of acute respiratory failure in hospitalised patients: a single-centre cohort study in the USA

“…1 Approximately 15% is bound to organic and inorganic anions, 40% is bound to proteins, particularly albumin, and 45% circulates as active ionised calcium. 2 This last portion is strictly controlled by parathyroid hormone and vitamin D. 3 Total serum calcium concentration substantially varies on the serum concentration of albumin and hydration status without any alteration in the concentration of ionised calcium. [4][5][6][7] Hence, measuring only total serum calcium might be misleading.…”

Diagnostic performance of predicted ionized calcium in dogs with total hypercalcemia and total hypocalcemia

“…A lack of correlation between tCa and miCa is of great concern in human and veterinary medicine. 17,18 In a general canine population, tCa appears poorly sensitive but quite specific for assessing calcium status, suggesting a high rate of false-negative results, but a few false-positive results based upon previous studies. 9,10 This contrasts with the present study, as only 55% of dogs with total hypercalcemia and 60% of dogs with total hypocalcemia had iHyperCa and iHypoCa, respectively.…”

“…Adjusting tCa for albumin or total protein concentrations is inefficient for this purpose. 9,10,17 A recent study evaluated a tCa threshold of 12 mg/dL in normophosphatemic dogs and found a high Spe, PPV, and NPV (100%, 93%, and 97%, respectively) for iHyperCa. This threshold, however, was inaccurate for confirming iHyperCa in hyperphosphatemic dogs owing to the low PPV (19%).…”