title: How do calcimimetics fit into the management of parathyroid hormone, calcium, and phosphate disturbances in dialysis patients?
abstract: As suggested by its American brand name (Sensipar), the calcimimetic cinacalcet sensitizes the parathyroid cells to the extracellular calcium signal, suppressing parathyroid hormone (PTH) release and synthesis and preventing parathyroid cell proliferation. This primary PTH suppression decreases the release of calcium and phosphate from bone without increasing intestinal absorption of calcium and phosphate. Therefore cinacalcet decreases the risk of hypercalcemia and hyperphosphatemia in contrast to 1alpha-OH vitamin D derivatives. Compared with calcium-containing oral phosphate binder (OPB), it increases the risk of hypocalcemia and may decrease the PTH-mediated phosphaturia in predialysis patients. This justifies its combined use with calcium-containing OPB in order to prevent hypocalcemia and enhance the hypophosphatemic effect of the latter, while improving PTH suppression. The National Kidney Foundation (NKF) Kidney Disease Outcomes Quality Initiative (K/DOQI) has recommended restriction of supplemental elemental calcium to 1.5 g/day, a recommendation that we believe should be revised. No pathophysiologic or randomized trial data have yet evidenced the absolute necessity for systematically using 1alpha-OH vitamin D derivatives and noncalcium-containing OPB rather than higher doses of calcium-containing OPB alone in uremic patients without vitamin D insufficiency. In patients with hyperparathyroidism as severe as in the "Treat to Goal Study," the Durham study showed that a calcium carbonate dose more than three times the K/DOQI limit could decrease PTH into the recommended range, with the advantage of a lower calcium-phosphate product compared with the combination of calcitriol and noncalcium OPB. Besides the efficient PTH suppression associated with lower calcium-phosphate product and a good gastrointestinal tolerance, long-term data suggest that cinacalcet may decrease the risk of parathyroidectomy and fracture, while high bone turnover lesions are improved. However, no long-term data on bone mineral density and cardiovascular calcification and complications are yet available. Such studies, along with those comparing cinacalcet and 1alpha-OH vitamin D-based approaches to hyperparathyroidism, are needed.
authors.affiliation: Nephrology Department, University Hospital, University Jules Verne, Amiens, France.
authors.forename: Irina
authors.initials: I
authors.lastname: Shahapuni
authors.forename: Janet
authors.initials: J
authors.lastname: Mansour
authors.forename: Laïd
authors.initials: L
authors.lastname: Harbouche
authors.forename: Bechir
authors.initials: B
authors.lastname: Maouad
authors.forename: Mohamed
authors.initials: M
authors.lastname: Benyahia
authors.forename: Khelifa
authors.initials: K
authors.lastname: Rahmouni
authors.forename: Roxana
authors.initials: R
authors.lastname: Oprisiu
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bonne
authors.forename: Matthieu
authors.initials: M
authors.lastname: Monge
authors.forename: Najeh
authors.initials: N
authors.lastname: El Esper
authors.forename: Claire
authors.initials: C
authors.lastname: Presne
authors.forename: Philippe
authors.initials: P
authors.lastname: Moriniere
authors.forename: Gabriel
authors.initials: G
authors.lastname: Choukroun
authors.forename: Albert
authors.initials: A
authors.lastname: Fournier
mesh_terms: D002118:Calcium / Q000378:metabolism*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000628:therapy*; D007676:Kidney Failure, Chronic / Q000150:complications; D009281:Naphthalenes / Q000494:pharmacology / Q000627:therapeutic use*; D010281:Parathyroid Hormone / Q000378:metabolism; D010758:Phosphorus / Q000378:metabolism*; D006435:Renal Dialysis
chemical_list: D009281:Naphthalenes; D010281:Parathyroid Hormone; D010758:Phosphorus; D002118:Calcium