Harmonisation of adjusted calcium equation, is it a realistic aim: a narrative review

Background and Objective: A prerequisite for harmonisation is the recognition and elimination of source(s) of variability in the system we aim to harmonise. The albumin-adjusted calcium equation is widely used and deeply rooted in current clinical practice. However, there are a number of well-recognised, scientifically-sound reasons and sources for variability in adjusted calcium determination. In this article, we review these factors contributing to adjusted calcium variability and explore a number of potential approaches to harmonisation. Methods: A search of EMBASE, Medline and PubMed Database was conducted with language restriction from the earliest publication date available to January 31, 2022. Key Content and Findings: The source of variations was summarised in three main categories related to the cumulative variation acquired from calcium/albumin measurements, the mathematical method(s) for equation derivation using these measurements, in addition to the inherent variability built-in the concept of adjusting calcium to albumin level. Conclusions: Variability in adjusted calcium results can be reduced by adopting a world-wide unified approach to several variables included in the adjusted calcium measurement. Further work is required for linearity of the range over which adjustment is made. However, standardisation of adjusted calcium is not achievable without improving the accuracy of albumin methods. Improvement work requires the collaborative efforts of laboratory medicine professional bodies and diagnostic companies.