Impact of etelcalcetide on fibroblast growth factor‐23 and calciprotein particles in patients with secondary hyperparathyroidism undergoing haemodialysis

Abstract

Aim: Recently, we demonstrated the efficacy of etelcalcetide in the control of secondary hyperparathyroidism (SHPT). This post hoc analysis aimed to evaluate changes in fibroblast growth factor-23 (FGF23) and calciprotein particles (CPPs) after treatment with calcimimetics. Methods: The DUET trial was a 12-week multicenter, open-label, parallel-group, randomized (1:1:1) study with patients treated with etelcalcetide plus active vitamin D (E + D group; n = 41), etelcalcetide plus oral calcium (E + Ca group; n = 41), or control (C group; n = 42) under maintenance haemodialysis. Serum levels of FGF23 and CPPs were measured at baseline, and 6 and 12 weeks after the start.Results: In the linear mixed model, serum levels of FGF23 in etelcalcetide users were significantly lower than those in non-users at week 6 (p < .001) and week 12 (p < .001). When compared the difference between the E + Ca group and the E + D group, serum levels of FGF23 in the E + Ca group were significantly lower than those in the E + D group at week 12 (p = .017). There were no significant differences in the serum levels of CPPs between etelcalcetide users and non-users at week 6 and week 12, while CPPs in the E + Ca group were significantly lower than those in the E + D group (p < .001) at week 12. Conclusion:Etelcalcetide may be useful through suppression of FGF23 levels among haemodialysis patients with SHPT. When correcting hypocalcaemia, loading oral calcium preparations could be more advantageous than active vitamin D for the suppression of both FGF23 and CPPs.

Effects of evocalcet on parathyroid calcium‐sensing receptor and vitamin D receptor expression in uremic rats

“…While combinations of Evo with high (≥1.5 μg/week) and low (<1.5 μg/week) doses of calcitriol produced equal suppression of iPTH, the high dose combination had a weaker effect on P and FGF23 levels than the low dose combination 30 . Etelcalcetide combined with high doses of calcitriol also showed a weak effect on the suppression of FGF23 and serum calciprotein particle levels 29 . Based on these reports, calcimimetics combined with low doses of VDRAs (in a case of calcitriol less than 1.5 μg/week) could be favorable for controlling MBD marker levels.…”

“…30 Etelcalcetide combined with high doses of calcitriol also showed a weak effect on the suppression of FGF23 and serum calciprotein particle levels. 29 Based on these reports, calcimimetics combined with low doses of VDRAs (in a case of calcitriol less than 1.5 μg/week) could be favorable for controlling MBD marker levels. In our study, Evo treatment slightly suppressed FGF23 levels and upregulated VDR, similar to Cina treatment.…”

“…[26][27][28] Recent studies have demonstrated that calcimimetics and low-dose VDRAs can simultaneously regulate MBD markers such as intact PTH (iPTH), Ca, P, and FGF23. 29,30 While combinations of Evo with high (≥1.5 μg/ week) and low (<1.5 μg/week) doses of calcitriol produced equal suppression of iPTH, the high dose combination had a weaker effect on P and FGF23 levels than the low dose combination. 30 Etelcalcetide combined with high doses of calcitriol also showed a weak effect on the suppression of FGF23 and serum calciprotein particle levels.…”

“…Interest in the suppressive effect of FGF23 has been growing because FGF23 is considered important in cardiovascular disease and mortality in CKD 26–28 . Recent studies have demonstrated that calcimimetics and low‐dose VDRAs can simultaneously regulate MBD markers such as intact PTH (iPTH), Ca, P, and FGF23 29,30 . While combinations of Evo with high (≥1.5 μg/week) and low (<1.5 μg/week) doses of calcitriol produced equal suppression of iPTH, the high dose combination had a weaker effect on P and FGF23 levels than the low dose combination 30 .…”

The effect of parathyroid hormone lowering by etelcalcetide therapy on calcification propensity and calciprotein particles in hemodialysis patients

“…As suggested by current KDIGO guidelines, we chose not to treat mild and asymptomatic hypocalcemia to avoid inappropriate calcium loading[ 24 ]. Moreover, no negative signals were associated with persistently low sCa levels in cinacalcet-treated patients of the EVOLVE trial[ 25 ] and a recent association study in incident hemodialysis patients failed to detect an increased mortality in dialysis patients with low sCa levels[ 26 ]. In accordance with previous studies using calcimimetics [ 5 , 7 , 21 , 27–30 ], etelcalcetide therapy was accompanied by significant reductions in serum levels of FGF-23 and also CTX.…”