What is Calcium Phosphate Product?
The calcium-phosphate product (Ca × P) is a calculated value obtained by multiplying serum calcium (mg/dL) by serum phosphorus (mg/dL), used primarily in chronic kidney disease to assess risk for vascular and soft tissue calcification, with values above 55 mg²/dL² associated with increased mortality and calcification risk. 1, 2
Definition and Calculation
The calcium-phosphate product is a mathematical calculation that multiplies the serum calcium concentration by the serum phosphorus concentration, both measured in mg/dL. 3 The resulting value is expressed in units of mg²/dL². 1
- When using total serum calcium, the traditional threshold values are 55 mg²/dL² (desirable goal) and 72 mg²/dL² (high risk). 1, 4
- When using ionized calcium measurements, corresponding values are 2.2 mmol²/L² and 2.8 mmol²/L², respectively. 3
Clinical Significance and Risk Stratification
The Ca × P product serves as a surrogate marker for the risk of extraskeletal calcification and mortality, particularly in patients with chronic kidney disease. 1, 2
Mortality Risk
In hemodialysis patients, the relationship between Ca × P product and mortality is dose-dependent:
- Patients with Ca × P product above 72 had a 34% higher relative risk of death compared to those with values between 42-52. 1
- For every 10-unit increase in Ca × P product, there is an 11% increase in relative risk of death. 1
Vascular Calcification Risk
The evidence linking Ca × P product to vascular calcification shows:
- Ca × P values above 55 are associated with increased risk of soft tissue and vascular calcification. 1, 2, 4
- Hemodialysis patients with Ca × P of 63 ± 13 had significantly higher mitral annular calcification compared to those with 56 ± 13. 1
- Young adults on hemodialysis with Ca × P of 65 ± 10.6 had significantly higher coronary artery calcification than those with 56 ± 12.7. 1
Acute Kidney Injury Risk
In hospitalized patients without pre-existing kidney disease, elevated admission Ca × P product independently predicts acute kidney injury:
- Ca × P ≥37 mg²/dL² was associated with increased AKI risk (OR 1.53-1.63). 5
- The incidence of AKI increased progressively from 11.1% in patients with Ca × P <22 to 19.9% in those with Ca × P ≥42. 5
Clinical Application and Target Goals
The K/DOQI guidelines recommend maintaining Ca × P product below 55 mg²/dL² to minimize calcification risk and potentially reduce mortality. 1, 2, 4
Management Strategy
When Ca × P product exceeds 55:
- Reduce phosphorus intake through dietary restriction and phosphate binders. 2, 6
- Limit calcium-based phosphate binders to under 1,500 mg/day of elemental calcium to avoid excessive calcium load. 1, 6
- Consider non-calcium phosphate binders (such as sevelamer) when hypercalcemia exists or total calcium intake becomes excessive. 1, 2
- Avoid calcium-based binders entirely in patients with low PTH (low-turnover bone disease), hypercalcemia, or severe vascular calcification. 1
Important Caveats and Limitations
Scientific Controversy
The validity of Ca × P product as an independent risk factor has been questioned in the literature. 7 The concept assumes that ectopic calcification results simply from supersaturation, which oversimplifies the complex biology of vascular calcification. 7
- Some studies show no independent association between Ca × P product and mortality after adjusting for GFR and other confounders in CKD stages 3-4. 8
- The chemistry underlying the use of the product is oversimplified, and experimental support for specific threshold values is limited. 7
Clinical Context Matters
- Not all patients with elevated Ca × P develop calcification, suggesting other factors play important roles. 1
- The relationship between Ca × P and calcified coronary plaque is significant, but the association with non-calcified plaque is weaker. 9
- Focusing solely on Ca × P without considering individual calcium and phosphorus levels can lead to suboptimal management. 2