The effectiveness of cinacalcet: a randomized, open label study in chronic hemodialysis patients with severe secondary hyperparathyroidism

Abstract

Background: Secondary hyperparathyroidism (SHPT) is associated with high incidences of cardiovascular disease, bone fracture, and mortality. This study was conducted to demonstrate the effectiveness of cinacalcet treatment on chronic kidney disease-mineral bone disorder (CKD-MBD) markers in chronic hemodialysis patients with severe SHPT. Methods: In phase 1, 30 adult HD patients were randomized to cinacalcet or control groups for 12 weeks to explore the achievement of >30% reduction of iPTH. In phase 2, 45 patients were participated to further explore the effect of cinacalcet on CKD-MBD parameters for 24-week follow up and 12 additional weeks after cinacalcet discontinuation. Results: In phase 1, the baseline serum iPTH levels were not different [1374 (955, 1639) pg/mL in the control group vs. 1191 (1005, 1884) pg/mL in the cinacalcet group], the percentage of patients achieving iPTH target were significantly higher in the treatment group [80% vs. 13%, p = .001]. In phase 2, the significant reductions of iPTH, FGF-23, tartrate-resistant acid phosphatase 5b, and slightly decreased size of parathyroid gland and stabilized vascular calcification were observed at 24-week follow up and markedly rebounded after discontinuation of cinacalcet. Conclusions: The effectiveness of cinacalcet were still obviously demonstrated even in chronic HD patients with severe SHPT. In addition, the improvements of bone markers and FGF-23, and stabilization of vascular calcification were observed. Therefore, cinacalcet can provide salutary effects on CKD-MBD in severe SHPT and might be an initially effective PTH-lowering therapy prior to surgical parathyroidectomy as well as an alternative treatment in the patients unsuitable for surgery. Clinical trial registration: ClinicalTrials.gov: NCT02056730. Date of registration: February 4, 2014.

<p>Efficacy and Safety of Evocalcet Evaluated by Dialysate Calcium Concentration in Patients with Secondary Hyperparathyroidism Undergoing Hemodialysis</p>

“…The present results showed that the FGF23 level decreased to approximately 50% in all sub-groups of each arm, which is consistent with the EVOLVE study of cinacalcet. 28 However, the FGF23 levels were somewhat variable, which is consistent with previous studies, 24,26,27 indicating that other factors, likely uncontrolled for in the present analysis and in previous studies, may be involved in the regulation of serum intact FGF23 level. Given the accumulating evidence to suggest a significant association between elevated FGF23 and cardiovascular disease, [28][29][30] the decreasing trend in FGF23 level observed after treatment with evocalcet and cinacalcet may be a beneficial effect.…”

“…These findings are consistent with those observed following treatment with other calcimimetics. 26,27 Although further studies are needed, evocalcet and cinacalcet appear to improve bone metabolism with dialysate calcium concentrations of 2.5 to 3.0 mEq/L.…”

Cinacalcet use in pediatric chronic kidney disease

“…22 Hyperphosphatemia in dialysis patients continues to represent a major challenge, and there is evidence associating serum phosphate concentrations with mortality. 23 The majority of the respondents used cinacalcet for cases of refractory hyperparathyroidism (48.5 %), or for cases of hyperparathyroidism with hypercalcemia (39%). However, a significant percentage of the respondents were using cinacalcet as second agent (9%).…”

“…Existing treatment strategies have the potential to elevate serum levels of calcium, which is considered an independent predictor of poor cardiovascular outcomes as a result of metastatic calcification. 23 The majority (77.8%) of nephrologists considered low serum calcium (<2.1 mmol/L) as a contraindication to commence cinacalcet while the remaining opted to use calcium supplements with cinacalcet in cases of hypocalcemia. It is widely accepted that hypocalcemia is a contraindication for cinacalcet use.…”

“…When the maintenance dose has been achieved, serum calcium and serum phosphorus should be evaluated monthly, and iPTH every 1 to 3 months. 23 There was a considerable percentage that observed side effects, or had to stop cinacalcet without controlling SHPT. Hypocalcemia, intestinal symptoms, myalgia and chest pain are possible side effects of cinacalcet.…”