In reply to Roberts

We thank Dr Roberts for his interest in our paper. The equation for adjusted calcium is based on three main factors: the population mean for calcium, and the intercept and slope of the relationship between calcium and albumin. These three factors vary between populations and analytical methods. This is the underlying reason why we recommend that laboratories derive an equation using their own local data.¹

The proposal by Roberts that calcium should be normalized to a mean of 2.4 mmol/L (mid-point of the Harmony reference range) assumes that this value agrees with the population calcium mean. However, our data from 15 clinical laboratories show significantly lower means, with an inpatient population mean for calcium of ∼2.2 mmol/L and a primary care calcium population mean of ∼2.3 mmol/L.² We also showed that the calcium population mean has a major impact on the outcome of the adjusted calcium equation.²

When the normalized equation performance was tested against ionized calcium in 123 subjects, as described in our population-specific equation paper,³ the normalized equation overestimated calcium status in healthy individuals and failed to identify any of the nine hypocalcaemic subjects. The same finding was observed when the normalized equations for 15 hospitals were compared with inpatient equations derived using Payne’s criteria (Figure 1).

Figure 1.

The impact of normalized equations from various analytical methods on the prevalence of hypocalcaemia (a) and hypercalcaemia (b) in hospitalized patients.

Payne’s calcium equation is widely used and deeply rooted in current UK clinical practice. To date, and despite many criticisms of Payne’s equations, no viable replacement to estimate calcium has been identified. Ionized calcium is not a perfect alternative as it, too, is affected by the albumin concentration.⁴ Therefore, while adjusted calcium equations remain in use, we suggest that any deviation from Payne’s original criteria, such as the use of the normalization concept, is validated against ionized calcium measurement for various calcium methods and analytical platforms before wider application.