From the FDA Drug Label
Plasma iPTH levels were measured using the Nichols IRMA. The average baseline iPTH level by the Nichols IRMA was 712 pg/mL, with 26% of the patients having a baseline iPTH level > 800 pg/mL. Approximately 60% of patients with mild (iPTH ≥ 300 to ≤ 500 pg/mL), 41% with moderate (iPTH > 500 to 800 pg/mL), and 11% with severe (iPTH > 800 pg/mL) secondary HPT achieved a mean iPTH value of ≤ 250 pg/mL. In the primary efficacy analysis, 40% of the patients on cinacalcet and 5% of placebo-treated patients achieved an iPTH ≤ 250 pg/mL (p < 0. 001) These studies showed that cinacalcet reduced iPTH while lowering Ca x P, calcium, and phosphorus levels
The relationship between PTH (parathyroid hormone), phosphate, and PCT (which is not explicitly mentioned in the provided text but can be related to the context of kidney function and dialysis) can be inferred as follows:
- Cinacalcet reduces iPTH levels, which in turn can affect phosphate and calcium levels in the body.
- The reduction in iPTH is associated with a decrease in Ca x P product, indicating a potential decrease in phosphate levels.
- However, the exact relationship between PTH, phosphate, and PCT cannot be directly concluded from the provided text, as PCT is not explicitly mentioned.
- It is known that in patients with CKD (Chronic Kidney Disease), especially those on dialysis, managing PTH, phosphate, and calcium levels is crucial for bone and mineral metabolism.
- Cinacalcet is used to treat secondary hyperparathyroidism in patients with CKD on dialysis, which involves managing PTH levels to prevent complications such as bone disease and vascular calcification.
- The management of phosphate levels is also critical in these patients, as hyperphosphatemia can lead to various complications, including vascular calcification and bone disease.
- The provided text does not directly address the relationship between PCT and PTH or phosphate levels, so no conclusion can be drawn regarding PCT 1.
From the Research
Parathyroid hormone (PTH) plays a crucial role in regulating phosphate levels in the body, particularly through its effects on the proximal convoluted tubule (PCT) of the kidney, as evidenced by a study published in 2021 2.
PTH and Phosphate Regulation
PTH decreases phosphate reabsorption in the PCT by inhibiting the sodium-phosphate cotransporters (primarily NaPi-2a and NaPi-2c), which leads to increased phosphate excretion in urine and consequently lowers serum phosphate levels. This phosphaturic effect is a key component of PTH's function in maintaining calcium-phosphate homeostasis.
- The relationship between PTH and phosphate is critical in clinical settings for diagnosing and managing disorders of calcium and phosphate metabolism, such as hyperparathyroidism, chronic kidney disease, and various forms of rickets and osteomalacia.
- A study published in 2011 3 highlights the importance of phosphate control in patients with chronic kidney disease, emphasizing that achieving normal phosphorus levels is associated with distinct clinical benefits.
- Additionally, PTH indirectly affects phosphate levels by stimulating the production of calcitriol (1,25-dihydroxyvitamin D) in the kidney, which enhances intestinal absorption of both calcium and phosphate.
Clinical Management
The management of secondary hyperparathyroidism in stages 3 and 4 chronic kidney disease involves suppression of parathyroid hormone (PTH) to normal levels with active vitamin D therapy and phosphate binders, as recommended in a study published in 2008 4.
- Early detection of secondary hyperparathyroidism is critical for effective treatment, with approximately 40% of patients with stage 3 CKD and 80% of patients with stage 4 having secondary hyperparathyroidism due to low serum 1,25-dihydroxyvitamin D levels.
- Active vitamin D analogues, such as calcitriol, doxercalciferol, and paricalcitol, are effective in suppressing PTH, but have varying effects on serum calcium and phosphorus levels.
- The use of cinacalcet in treating secondary hyperparathyroidism in stages 3 and 4 CKD is limited, and it is only approved for use in patients receiving dialysis.