Use of Data Mining in the Establishment of Reference Intervals for Albumin-Adjusted Calcium

Background

Calcium homeostasis is critical for numerous physiological functions, and while total calcium is commonly measured in clinical practice, albumin-adjusted calcium is widely used to account for protein binding, despite concerns about its accuracy and lack of standardized reference intervals. This study aims to establish a reliable reference range for albumin-adjusted calcium using real-world data from a high-volume tertiary care laboratory.

Methods

This study analyzed data from 33,159 individuals aged 18–80 years, selected from an initial population of 106,920 patients based on specific biochemical and clinical exclusion criteria. Statistical analysis involved outlier detection, partitioning, and calculation of age-specific reference intervals using the 2.5th and 97.5th percentiles.

Results

The study established age-stratified reference intervals for albumin-adjusted calcium (18–49 years: 2.17–2.55 mmol/L; 50–79 years: 2.20–2.61 mmol/L) and total calcium (18–49 years: 2.17–2.56 mmol/L; 50–79 years: 2.17–2.62 mmol/L).

Conclusions

Our study reveals that albumin-adjusted calcium reference intervals are age-dependent, with slightly higher upper limits (≈0.05 mmol/L) than traditionally used total calcium ranges, potentially reducing overdiagnosis of hypercalcemia. Further studies are needed to validate these reference intervals across different automated analyzers and diverse patient populations to ensure broader clinical applicability.