What is phosphate?

Phosphate is an essential component of the human body and plays a crucial role in many physiological processes. The phosphate level in the blood is maintained by complex regulatory mechanisms that affect both the absorption and excretion of phosphate. Normally, the phosphate concentration in serum is between 2.5 and 4.5 mg/dl.

Phosphate is particularly important for the formation and maintenance of bone structure, as it combines with calcium to form hydroxyapatite, which strengthens bone tissue. In addition, phosphate is an important component of ATP (adenosine triphosphate), the main energy molecule in cells, and plays a role in cell division and cell growth.

Disorders of phosphate metabolism can lead to various health problems. High blood phosphate levels, also known as hyperphosphatemia, are often associated with the development of vascular calcification and cardiovascular disease. This is because excess phosphate can promote the formation of calcium phosphate deposits in blood vessels and other tissues. Studies have shown that elevated phosphate levels correlate with increased rates of coronary atherosclerosis, indicating a possible link between high phosphate levels and cardiovascular disease.

On the other hand, low phosphate levels, known as hypophosphatemia, can also pose health risks. This condition can lead to muscle weakness, bone mineralization and decreased cell function. Low phosphate levels may be due to inadequate dietary intake, increased renal excretion or certain medical conditions.

The regulation of phosphate levels in the body is a dynamic process influenced by several hormones and genetic factors. In particular, parathyroid hormone (PTH) and vitamin D play a crucial role in controlling phosphate absorption and excretion. PTH increases renal phosphate excretion, while vitamin D promotes intestinal phosphate absorption.

Impact on renal function

Blood phosphate levels have a profound effect on kidney function. Chronic excess phosphate can lead to kidney damage, as the kidneys are responsible for regulating and excreting phosphate. Sustained high phosphate levels can lead to increased formation of phosphate-calcium deposits in the kidneys, which can further impair kidney function. These deposits can reduce glomerular filtration rate and contribute to the worsening of kidney disease. High phosphate levels are associated with increased morbidity in patients with chronic kidney disease because the impaired kidney function is no longer able to efficiently excrete excess phosphate.

Did you know?

High phosphate levels not only put a strain on the bones and the cardiovascular system, but can also serve as an early indicator of impending kidney failure, even before other symptoms become visible.

Phosphate and cardiovascular health

The role of phosphate in cardiovascular health is another important area of research. High blood phosphate levels are associated with an increased risk of cardiovascular disease. This is mainly due to the fact that they promote vascular calcification. Elevated phosphate levels contribute to the formation of calcium phosphate deposits in the arterial walls, which leads to a deterioration in vascular elasticity and an increased risk of heart attack and stroke. One study showed that long-term exposure to high phosphate concentrations was significantly correlated with an increased rate of coronary atherosclerosis.

What does genetics have to do with it?

A notable SNP is rs1697421 in the ALPL gene, which influences the synthesis of alkaline phosphatase. This enzyme plays a central role in regulating phosphate levels in bone metabolism. Variations in this gene can lead to different phosphate levels in serum by altering alkaline phosphatase activity and thus influencing phosphate build-up and breakdown in the bone. The SNP rs17265703 in the CSTA gene, which codes for cystatin A, is also relevant. Cystatin A is a protease inhibitor and influences the regulation of phosphate metabolism by affecting the binding and release of phosphate in the body. Genetic variations in CSTA can therefore lead to different phosphate levels by affecting the amount of available phosphate. Another significant SNP is rs9469578 in the IHPK3 gene, which codes for inositol hexakisphosphate kinase 3. This enzyme is involved in phosphate regulation and signal transduction in cells. Variations in this gene can affect phosphate uptake and utilization in different cell types, thereby altering blood phosphate levels. rs947583 in the PDE7B gene, which codes for phosphodiesterase 7B, also plays a role. Phosphodiesterases are enzymes that are responsible for the breakdown of cyclic nucleotides and thus indirectly influence phosphate regulation. Genetic variations in PDE7B can affect phosphate levels by altering the metabolism of these nucleotides. Finally, the SNP rs2970818 affects the FGF6 gene, which codes for the fibroblast growth factor 6. FGF6 is involved in the regulation of bone growth and phosphate utilization. Genetic variants in this gene can influence the efficiency of bone mineralization and thus the phosphate level in the serum.