Standardisation of Adjusted Calcium Equation: the UK Approach—a Narrative Review

Background and Objective: Adjusted serum calcium in the UK has, since the 1970s, almost exclusively been calculated in relation to the serum albumin level measured on the same specimen. Since 1973 various adjustment equations have been derived and reported in the literature. More recently, laboratory information systems have allowed laboratories easily to derive their own adjustment equations. Both Pathology Harmony UK and The Association for Clinical Biochemistry and Laboratory Medicine (ACB) have proposed similar protocols for laboratories to follow to achieve this aim. The objective of this review is to investigate the various strategies for adjustment of calcium and compare their performance for assessment of physiological calcium status against actual (unadjusted) and ionised calcium. Methods: Papers to be included in the review were identified from a Google Scholar search using the terms adjusted calcium, ionised calcium and albumin from 1973, when the use of calcium adjustment for albumin level was first documented, until May 2022. The search was limited to English language papers, but not to the UK. Information from questionnaires from the Keele Benchmarking project (2008) and from the Wales External Quality Assessment Scheme (WEQAS) was accessed as was WEQAS quality assurance data for adjusted calcium for the period 2008–2022 Key Content and Findings: There is evidence from the UK that locally based adjustment equations provide better consensus values for adjusted calcium in external quality assurance (EQA) schemes. Locally derived adjustment equations also provide better classification of patient status than the use of generic equations from the literature. There is still dispute about how well adjustment equations perform in patients with significant physiological disturbances, e.g., acute acidosis, end-stage renal failure. The importance of deriving a suitable valid reference range for adjusted calcium is still not appreciated in several recent papers in the literature. Conclusions: This review has revealed an increase in the use of locally derived calcium equations in the UK; this has resulted in better assessment of calcium status than the use of generic equations. Various novel options for further improvement in performance of the adjustment equations may prove advantageous in certain specialist areas such as renal dialysis. More studies are required on the use of ionised calcium to validate adjustment equations: this should inform the future strategy either to further refine calcium adjustment or to promote increased use of ionised calcium measurement.