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

Abstract Background This study investigated whether parathyroid hormone (PTH) lowering with etelcalcetide, and the consequent effects on mineral and bone metabolism, could improve serum calcification propensity (T50 time) and decrease calciprotein particle (CPP) load in hemodialysis patients with secondary hyperparathyroidism. Methods In this single-arm, prospective, dose-escalation proof-of-principle study, hemodialysis patients received etelcalcetide at 2.5 mg/dialysis session with increments of 2.5 mg every four weeks to a maximum dose of 15 mg thrice weekly or until a pre-specified safety endpoint was reached, followed by an eight-week washout phase. Results Out of 36 patients recruited (81% male, 62±13 years), 16 patients completed the study per protocol with a mean maximum tolerated dose of etelcalcetide of 9.5±2.9 mg/dialysis session. With escalating doses of etelcalcetide, PTH and serum calcium levels significantly decreased (p<0.0001). While there was no significant change in T50 times or serum phosphate levels, etelcalcetide did yield significant and consistent reductions in serum levels of endogenous calciprotein monomers [-35.4 (-44.4 to -26.5)%, p<0.0001], primary [-22.4 (-34.5 to -10.3)%, p<0.01] and secondary CPP [-29.1 (-45.7 to -12.4)%, p<0.01], an effect that was reversed after therapy withdrawal. Serum levels of osteoclastic markers significantly decreased with escalating doses of etelcalcetide, while levels of the osteoblastic marker remained stable. Conclusions Lowering of PTH with etelcalcetide did not result in statistically significant changes in T50. In contrast, homogenous reductions in serum levels of calciprotein monomers, primary and secondary CPP were observed.