From the Guidelines
Increased phosphate levels in the blood (hyperphosphatemia) lead to metastatic calcification by disrupting calcium-phosphate homeostasis and causing abnormal mineral deposition in normal tissues. When phosphate levels rise, they combine with calcium to form calcium phosphate crystals that precipitate in soft tissues throughout the body. This process begins when the calcium-phosphate product (serum calcium × phosphate) exceeds 55-60 mg²/dL², as noted in studies such as 1. The excess phosphate also stimulates parathyroid hormone secretion and reduces vitamin D activation, further destabilizing mineral balance. Additionally, elevated phosphate directly damages vascular smooth muscle cells, causing them to transform into osteoblast-like cells that promote calcification. Common sites for metastatic calcification include:
- Blood vessels
- Kidneys
- Lungs
- Gastric mucosa
- Corneas This process is particularly problematic in chronic kidney disease patients, where phosphate binders like sevelamer, calcium acetate, or lanthanum carbonate are often prescribed to reduce phosphate absorption, as discussed in 1. Dietary phosphate restriction (800-1000 mg/day) is also recommended. The underlying mechanism involves disruption of inhibitory proteins like fetuin-A and matrix Gla protein that normally prevent inappropriate calcification, allowing mineral crystals to form and deposit in tissues where they shouldn't normally occur. It is essential to focus treatment on patients with hyperphosphatemia, rather than maintaining normal phosphate levels in all patients, as suggested by the current evidence 1. Prevention rather than treatment of hyperphosphatemia may be valuable in patients with CKD stage G3a to G5D, but future studies will need to address the potential value of hyperphosphatemia prevention in at-risk CKD populations.
From the Research
Mechanism of Metastatic Calcification
- Metastatic calcification occurs when there is an imbalance of calcium and phosphate in the body, leading to the deposition of calcium salts in soft tissues such as arteries, skin, and organs 2, 3.
- Hyperphosphatemia, or elevated phosphate levels, is a key factor in the development of metastatic calcification, as it can lead to an increase in the calcium-phosphate product, which promotes calcification 2, 3.
- The use of calcium-containing phosphate binders can exacerbate metastatic calcification by increasing the absorption of calcium and perpetuating the calcium-phosphate product 4, 5.
Effects of Hyperphosphatemia
- Hyperphosphatemia can lead to secondary hyperparathyroidism, which can further contribute to metastatic calcification by increasing parathyroid hormone (PTH) levels and promoting bone resorption 2, 3.
- Elevated PTH levels can also lead to an increase in calcium levels, which can further contribute to metastatic calcification 2, 3.
- Control of serum phosphate is crucial in preventing increases in calcium x phosphate product, secondary hyperparathyroidism, and ultimately vascular calcification 3.
Treatment and Management
- The use of non-calcium-containing phosphate binders, such as sevelamer hydrochloride, may be beneficial in reducing the risk of metastatic calcification and mortality in patients with chronic kidney disease 4, 5.
- Tight control of calcium and phosphate levels, as well as the use of low-calcium dialysate and parathyroidectomy, may also be effective in managing metastatic calcification 2, 6.
- Avoiding the overzealous use of active vitamin D therapy in patients with uncontrolled hyperparathyroidism is also important in preventing metastatic calcification 6.