What is the relationship between albumin and calcium levels in the blood?

From the Guidelines

Albumin and calcium levels in the blood have a crucial interdependent relationship, with approximately 40-50% of total calcium bound to albumin, and this relationship significantly impacts the interpretation of calcium measurements in patients with abnormal albumin levels. The binding of calcium to albumin is a key aspect of calcium homeostasis, with albumin containing negatively charged binding sites that attract positively charged calcium ions, creating a reservoir of calcium that can be released when needed 1.

When albumin levels decrease, such as in hypoalbuminemia, the total serum calcium measurement may appear falsely low, even though the physiologically active ionized calcium remains normal. For every 1 g/dL decrease in serum albumin below 4 g/dL, the total calcium decreases by approximately 0.8 mg/dL 1. This relationship is clinically significant because physicians must adjust calcium measurements in patients with abnormal albumin levels to accurately assess calcium status. Without this correction, patients with low albumin might be incorrectly diagnosed with hypocalcemia when their ionized calcium is actually normal.

Some key points to consider in the relationship between albumin and calcium include:

• The importance of correcting total calcium measurements for abnormal albumin levels to accurately assess calcium status
• The use of formulas to correct total calcium for abnormal albumin or to calculate free calcium, although these formulas have limitations 1
• The impact of pH changes on ionized calcium levels, with a fall in pH causing an increase in ionized calcium and alkalosis decreasing free calcium by enhancing binding of calcium to albumin 1
• The lack of biochemical measurements that reflect calcium nutritional status, with indirect measures such as skeletal health and bone mass measurements used to assess calcium adequacy 1.

In clinical practice, understanding the relationship between albumin and calcium is essential for accurately interpreting calcium measurements and making informed decisions about patient care. Physicians should prioritize adjusting calcium measurements for abnormal albumin levels to ensure accurate assessment of calcium status and prevent misdiagnosis of hypocalcemia or hypercalcemia.

From the FDA Drug Label

12.3 Pharmacokinetics ... Distribution ... approximately 40% is protein-bound (primarily to albumin) The relationship between albumin and calcium levels in the blood is that about 40% of total serum calcium is protein-bound, primarily to albumin.

• Albumin binds to calcium in the blood, affecting the total serum calcium level.
• The biologically active part of calcium is the ionized form, which is about 50% of total serum calcium 2.

From the Research

Relationship Between Albumin and Calcium

The relationship between albumin and calcium levels in the blood is complex, with albumin binding to calcium and affecting its measurement.

• Albumin-adjusted calcium measurements are commonly used, but studies have shown that this adjustment may not always be necessary or accurate 3, 4, 5.
• The correlation between albumin and ionized calcium levels has been found to be significant, but the effect of albumin on ionized calcium measurements is relatively small and may not be clinically important in most situations 4.
• In patients with hypoalbuminemia, the use of albumin-adjusted calcium measurements may lead to errors in estimating ultrafilterable calcium concentrations, and ionized calcium measurements may be more accurate 6.

Factors Influencing the Relationship

Several factors can influence the relationship between albumin and calcium, including:

• The type of analyzer used to measure ionized calcium 4
• The presence of hypoalbuminemia, which can affect the binding of calcium to albumin 6
• The use of different adjustment formulas, which can have varying degrees of accuracy 3, 7, 5
• The patient's kidney function, with decreased kidney function potentially affecting the accuracy of albumin-adjusted calcium measurements 5

Clinical Implications

The clinical implications of the relationship between albumin and calcium are significant, as accurate measurement of calcium levels is crucial for diagnosis and treatment of various conditions.

• Unadjusted total calcium measurements may be more accurate than albumin-adjusted measurements in some cases, particularly in patients with hypoalbuminemia or decreased kidney function 3, 5.
• Ionized calcium measurements may be more accurate than albumin-adjusted measurements, but are often more difficult to obtain due to strict preanalytical and analytical requirements 7.
• The use of albumin-adjusted calcium measurements should be approached with caution, and clinicians should consider the potential limitations and errors associated with these measurements 3, 4, 7, 5.