A medication called cinacalcet—an important part of treatment to control high levels of parathyroid hormone (PTH) in patients receiving dialysis for end-stage renal disease (ESRD)—works by resetting the balance between calcium and PTH levels, according to a study in the November Journal of the American Society of Nephrology (JASN).
Cinacalcet is one of a family of drugs called calcimimetics. "In hemodialysis patients, the use of calcimimetics decreases the set point of the PTH-calcium curve, which means that PTH secretion by cells is suppressed at low or normal calcium levels," comments Mariano Rodriguez, MD, PhD, of Nephrology Service, Hospital Universitario Reina Sofia in Cordoba, Spain.
Dr. Rodriguez and colleagues studied responses to cinacalcet treatment in nine patients with ESRD receiving long-term hemodialysis to replace lost kidney function. All patients had high levels of PTH, or secondary hyperparathyroidism—a frequent complication of kidney disease that is mainly caused by low calcium levels. Hyperparathyroidism can lead to weakening of the bones and other problems, including cardiovascular disease.
The researchers assessed the "PTH-calcium curve," which reflects the way PTH levels respond to calcium levels, by comparing blood samples obtained during dialysis performed at low and high calcium levels. The study took advantage of a new test that provides more complete information on the dynamics of PTH secretion.
Treatment with cinacalcet led to significant reductions in the patients' blood phosphorus levels. Their levels of PTH before dialysis were also decreased.
Cinacalcet also led to a reduction in the set point of the PTH-calcium curve. This occurred because cinacalcet made parathyroid cells more sensitive to calcium.
The study provides important new information on how cinacalcet and other calcimimetic drugs work to reduce PTH levels. Normally, low calcium levels cause cells to increase secretion of PTH. After cinacalcet treatment, PTH secretion doesn't increase even when calcium levels are low. Cinacalcet doesn't just lower calcium and PTH levels in the short term, the new results suggest—it changes the interaction between calcium and PTH levels in the long term.
Secondary hyperparathyroidism is a common and potentially serious problem in patients with kidney disease. Calcimimetic drugs like cinacalcet provide a valuable new treatment option. "Nowadays the calcimimetics are an essential tool in the treatment of secondary hyperparathyroidism," says Dr. Rodriguez. "With these drugs, the need for surgery to remove the parathyroid gland (parathyroidectomy) is markedly decreased."
The results provide nephrologists with new insights into the way cinacalcet works to control PTH levels in ESRD patients with hyperparathyroidism. "High PTH levels and the excess of calcium in blood are easy to control with calcimimetics," Dr. Rodriguez adds.
The study was limited by the lack of data on the effects of cinacalcet in patients on peritoneal dialysis, although there are no reasons to believe that results would have been different in peritoneal dialyisis patients. In addition, the patients in the study were not taking vitamin D, another effective treatment for hyperparathyroidism. "It would have been interesting to evaluate the combined effect of calcimimetics and vitamin D on the set point of the PTH-calcium curve," says Dr. Rodriguez.
Funding was provided by Government grants from instituto Carlos III, Consejeria de Salud de la Junta de Andalucia and Fundación Nefrologica and Red de Investigación Renal. Funding for the writing was provided by Amgen Europe.
The article, entitled "Cinacalcet Reduces the Set Point of the Parathyroid Hormone -Calcium Curve in Hemodialysis Patients with Secondary Hyperparathyroidism," will appear online at http://jasn.asnjournals.org/ on July 16, 2008, and in print in the November 2008 issue of JASN.
ASN is a not-for-profit organization of 11,000 physicians and scientists dedicated to the study of nephrology and committed to providing a forum for the promulgation of information regarding the latest research and clinical findings on kidney diseases. ASN publishes JASN, the Clinical Journal of the American Society of Nephrology (CJASN), and the Nephrology Self-Assessment Program (NephSAP). In January 2009, the Society will launch ASN Kidney News, a newsmagazine for nephrologists, scientists, allied health professionals, and staff.
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Journal of the American Society of Nephrology