From the Guidelines
Ionized calcium and total serum calcium are two distinct measures of calcium in the blood, with ionized calcium being the biologically active form and total serum calcium including both ionized and bound fractions.
Key Differences
- Ionized calcium, also known as free calcium, is the fraction of calcium that is not bound to proteins and is available for physiological processes, with normal values ranging from 4.65 to 5.28 mg/dL (1.16 and 1.32 mmol/L) in adults 1.
- Total serum calcium, on the other hand, includes both ionized and bound fractions, with approximately 40% bound to proteins, 48% as free calcium, and 12% complexed with anions such as phosphate and citrate 1.
Clinical Significance
- In patients with chronic kidney disease (CKD), total serum calcium levels may need to be adjusted for albumin levels to accurately reflect the free calcium concentration, using formulas such as Corrected total calcium (mg/dL) = Total calcium (mg/dL) + 0.8 [4 Serum albumin (g/dL)] 1.
- Maintaining normal serum levels of corrected total calcium is important in CKD patients, with the goal of keeping levels within the normal range for the laboratory used 1.
Measurement Considerations
- Ionized calcium can be measured using ion-selective electrodes, but this method is not routinely used due to its time-consuming and expensive nature, as well as variability in reproducibility 1.
- Total serum calcium measurements are more commonly used, but may not accurately reflect free calcium levels in patients with abnormal albumin levels or other conditions that affect calcium binding 1.
From the Research
Difference between Ionized Calcium and Total Serum Calcium
- Ionized calcium (iCa) is the biologically active fraction of calcium in the blood, whereas total serum calcium (tCa) includes both ionized and bound calcium [ 2 ].
- Serum tCa does not accurately predict iCa status in many clinical conditions, and direct measurement of iCa is necessary for accurate assessment [ 2 ].
- Ionized calcium cannot be reliably predicted from total calcium, and there is a significant difference between ionized and total calcium in many patients [ 3 ].
Clinical Significance
- Ionized calcium is a more sensitive index of calcium metabolism than total serum calcium [ 3 ].
- Measurement of ionized calcium is more important than measurement of total calcium in serum samples, especially in patients with suspected calcium disorders [ 4 ].
- Diagnostic discordance between serum total calcium and measured ionized calcium can occur in up to 31% of patients, highlighting the need for direct measurement of ionized calcium [ 5 ].
Measurement and Analysis
- Anaerobic measurement of serum iCa under controlled conditions provides the most reliable assessment of calcium status [ 2 ].
- Automated routine measurement of serum adjusted ionized calcium (at pH 7.4) can be used for routine analysis of serum adjusted Ca2+ (at pH 7.4) [ 6 ].
- Total calcium is a less accurate test in predicting ionized calcium, and there is a very poor agreement between total calcium and adjusted ionized calcium in many samples [ 6 ].