#2035 Use of ETElcalcetidefor pReserving vitamiN K-dependent proteInactivitYITAlian Study (ETERNITY-ITA Study)
Authors: Fusaro Maria , Gallieni Maurizio , Sartò Giulia Vanessa Re , Cossettini Althea , Cosmai Laura , Marino Carmela , Aghi Andrea , Tripepi Giovanni Luigi 
Published: May 2024

Abstract

Background and Aims
Vascular calcifications (VCs) are prevalent in chronic kidney disease (CKD) and mineral disorders, associated with aortic calcification and increased bone fracture risk. The complex pathogenesis involves factors like calcium overload, phosphate imbalance, and secondary hyperparathyroidism. Key inhibitors, vitamin K-dependent proteins (VKDPs) like matrix Gla protein (MGP) and osteocalcin (BGP), play pivotal roles in VC development. Traditional VC risk reduction focuses on lowering parathyroid hormone, calcium and phosphorus levels. Etelcalcetide, a synthetic peptide activating the calcium-sensing receptor, demonstrates promise in clinical trials. Studies on Vitamin K Italian (VIKI) show that calcimimetic treated hemodialysis patients exhibit higher levels of total BGP and MGP, suggesting a protective effect. These findings underscore the multifactorial nature of VC in CKD, informing refined treatment strategies and targeted pathways for improved outcomes. The proposed study will investigate real world evidence of the effect of Etelcalcetide in preserving active forms of VKDPs among total MGP and total BGP with a resulting reduction of those inactive such as dephosphorylated-undercarboxylated MGP or dp-uc MGP, undercarboxylated BGP or uc-BGP, thus contributing to bone and vascular health in hemodialysis patients (Table 1).

Method
This is a multi-center comparative effectiveness observational longitudinal study with no predefined interference on drug dosing on the part of the investigators. The study will enroll 160 hemodialysis patients: 80 patients considered in the exposed group (treated with Etelcalcetide) and 80 age and sex matched patients considered in the unexposed group (treated with Calcitriol or vitamin D analogs). The treating nephrologist will base their target dose of Etelcalcetide on an individual-level patient basis in order to achieve the KDIGO PTH target level. In the Etelcalcetide-treated group, the addition of calcitriol is allowed when required by normal clinical practice (for correction of hypocalcemia) (Fig. 1).
The primary endpoint is the comparison of the levels of active and non-active forms of VKDP between patients treated with Etelcalcetide and those treated with vitamin D or vitamin D analogues.
The two groups will be compared for longitudinal changes in the following biomarkers, measured at baseline and after 3, 9, and 18 months of treatment: total MGP, dephosphorylated-undercarboxylated MGP, total BGP, and undercarboxylated BGP. As secondary outcomes will be evaluated bone vascular markers levels, serum calcification propensity T50 test, anemia markers levels, dialysis routine biomarkers, changes from baseline prevalence VCs (Aorta and Iliac arteries) and vertebral fractures by lateral Dorsal Lumbar spine x-Ray and Bone Mass Density (BMD) by Dual-energy X-ray absorptiometry (DEXA).

Results

Conclusion