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Cinacalcet reduced serum calcium in hemodialysis patients with hyperparathyroidism
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In hemodialysis patients with secondary hyperparathyroidism, cinacalcet (Sensipar, Amgen), a calcimimetic, may increase the parathyroid’s sensitivity to calcium and cause a reduction in the set point of the parathyroid hormone-calcium curve.
Researchers from the Hospital Universitario Reina Sofia in Cordoba, Spain examined the effect of cinacalcet on the parathyroid hormone-calcium curve in nine long-term hemodialysis patients with secondary hyperparathyroidism.
The patients were assigned to two months of cinacalcet, titrated based on parathyroid hormone and concentrations of plasma calcium, according to the researchers.
The researchers created curves to demonstrate the way parathyroid hormone levels respond to calcium levels. They used blood samples obtained during dialysis at low-calcium (0.75 mM) and high-calcium (1.75 mM) dialysate. According to the researchers, mean serum calcium, intact parathyroid hormone and whole parathyroid hormone significantly reduced as a result of cinacalcet, compared to cinacalcet levels at baseline (P<.001).
Cinacalcet also reduced set points for parathyroid hormone-calcium curves and minimum and maximum levels of parathyroid hormone. – by Stacey L. Adams
J Am Soc Nephrol. 2008;doi:10.1681/ASN.2007121320.
This study explores the dynamics of the relationship between serum calcium and parathyroid hormone in dialysis patients with secondary hyperparathyroidism before and after a two-month course of the calcimimetic cinacalcet. Cinacalcet is thought to increase the sensitivity of the calcium-sensing receptor to calcium and is approved for the treatment of secondary hyperparathyroidism. The calcium concentration of the dialysate was varied and an in vivo curve of serum-ionized calcium and parathyroid hormone generated, allowing for the calculation of a calcium concentration set point. Cinacalcet clearly reduced the set point towards normal and shifted the calcium-parathyroid hormone curve to the left. Assays were performed to measure both the standard intact parathyroid hormone as well as an assay specific for the bioactive form (whole parathyroid hormone). Non-bioactive parathyroid hormone is often disproportionately elevated in renal failure. The influence of cinacalcet to reduce the set point was seen for both the intact parathyroid hormone as well as the bioactive form of parathyroid hormone. These findings provide important insights into the mechanism of cinacalcet action in the treatment of hyperparathyroidism. Primary hyperparathyroidism is also associated with a rightward shift in the calcium-parathyroid hormone curve and an increase in the calcium set point. Cinacalcet likely has a similar mode of action in lowering parathyroid hormone and serum calcium in primary hyperparathyroidism, but it is more difficult to vary serum calcium concentration in this setting and directly measure the set point.
– Gregory A. Brent, MD
Endocrine Today Editorial Board member