Viewpoint: 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.

Long-Term Outcomes of Cinacalcet and Paricalcitol Titration Protocol for Treatment of Secondary Hyperparathyroidism

“…Calcium-based phosphate binder use and the average dose increased in our study, but serum Ca decreased, consistent with a previous observation [9]. In the phase III cinacalcet trials, more patients on cinacalcet were started on calcium-based binders, but their mean dose was unchanged [5,6,7].…”

“…Some suggest instituting cinacalcet if iPTH remains between 300 and 800 pg/ml despite traditional therapy [9]. Combination therapy, from both a pathophysiological and clinical perspective, may be more advantageous, utilizing several different mechanisms in treating resistant disease [10].…”

Bone mineral density and parathyroid function in patients on maintenance hemodialysis

“…[35,36] It has been suggested that a different target PTH range should be used in patients with versus those without significant aluminum deposition in the bone. [37] Data from patients without evidence of aluminum intoxication on bone biopsy were analyzed in a study in Toronto [20].…”

Simultaneous Control of PTH and Ca×P Is Sustained over Three Years of Treatment with Cinacalcet HCl

“…Treatment with cinacalcet hydrochloride (cinacalcet) often concurrently lowers PTH, Ca, P, and CaϫP levels among dialysis patients with SHPT (11)(12)(13)(14). Its use can provide sustained control of key biochemical parameters in those receiving traditional treatments for SHPT as judged by the achievement of values within the target ranges recommended by the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI TM ) (15).…”