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Sir, Parathyroid cells can sense small changes in plasma calcium ion (Ca2+) levels by virtue of a cell surface calcium receptor (CaR). Calcimimetics such as R-568 and cinacalcet hydrochloride (cinacalcet) are positive allosteric modulators that activate CaRs and thereby suppress parathyroid hormone (PTH) secretion [1]. Clinical trials have demonstrated that cinacalcet treatment lowers not only the serum PTH but also the serum Ca levels in haemodialysis (HD) patients with secondary hyperparathyroidism (2HPT) [1]. In clinical use, the dosage of cinacalcet is not restricted by the time of the HD session because HD does not affect the pharmacokinetics of this compound [2]; this is attributed to cinacalcet’s high binding capacity to plasma proteins. The use of a so-called low-Ca dialysate (2.5 mEq/L) can increase the usage opportunities and doses of vitamin D drugs and Ca-containing phosphate binders. During each HD session, diffusion is the main route of Ca2+ transport, and the rate of passage of a given dialysate Ca2+ across the membrane depends on the direction and magnitude of its concentration gradient between the blood and dialysate [3]. Therefore, many HD patients show a transient elevation in serum PTH levels in response to the decreased plasma Ca2+ levels at the end of every HD session with a low-Ca dialysate [4]. In our experience, injection of calcitriol or its analogue (maxacalcitol) just before the HD session has failed to suppress this elevation in PTH levels. Here, we report that if cinacalcet is administered just before an HD session, it successfully suppresses the increase in the intact PTH (i-PTH) induced by a low-Ca dialysate. The subjects of this study were 14 HD patients (9 female subjects) with a mean age of 58.5 ± 9.0 (SD) years and an HD vintage of 19.8 ± 9.4 (SD) years. All the patients had been diagnosed as 2HPT with parathyroid gland (PG) nodular hyperplasia on the basis of the findings of ultrasonography (maximum PG volume ≥ 500 mm3 or maximum PG diameter ≥ 10 mm) and had been treated with intravenous calcitriol or maxacalcitol. Before the cinacalcet treatment started, an HD session (2.5 mEq/L Ca dialysate, 4 h in 10 patients and 4.5 h in 4 patients) significantly decreased the plasma Ca2+ levels and increased the serum i-PTH levels (Figure 1A). One week after the cinacalcet treatment Fig. 1. Plasma Ca2+ and serum i-PTH levels just before (Pre-HD) and after (Post-HD) an HD session (2.5 mEq/L Ca dialysate, for 4 or 4.5 h). (A) The changes in Ca2+ and i-PTH after the HD without cinacalcet. (B) One week after cinacalcet treatment (25 mg, daily). Cinacalcet (25 mg) was administered just before an HD session, and the Ca2+ and i-PTH were examined at Preand Post-HD. (C) Four weeks after the cinacalcet treatment (25 mg, daily). Cinacalcet (25 mg) was administered just before an HD session, and the Ca2+ and i-PTH levels were examined at Preand Post-HD. All data are expressed as the mean ± SD (n = 14). ∗P < 0.05, ∗∗P < 0.01 versus the values at Pre-HD (paired t-test).

clinical kidney journal

The administration of cinacalcet hydrochloride just before a haemodialysis session suppresses the transient rise in intact parathyroid hormone induced by a low-calcium dialysate: when should cinacalcet hydrochloride be administered?