Abstract
BackgroundSecondary hyperparathyroidism (sHPT), a complication of chronic kidney disease (CKD) characterized by persistently elevated parathyroid hormone (PTH), alterations in calcium-phosphorus homeostasis, and vitamin D metabolism, affects 50% of children receiving dialysis. A significant proportion of these children develop CKD-mineral and bone disorder (CKD-MBD), associated with an increased risk of fractures and vascular calcification. The standard of care for sHPT in children includes vitamin D sterols, calcium supplementation, and phosphate binders. Several agents are approved for sHPT treatment in adults undergoing dialysis, including vitamin D analogs and calcimimetics, with limited information on their safety and efficacy in children. The calcimimetic cinacalcet is approved for use in adults with sHPT on dialysis, but is not approved for pediatric use outside Europe.MethodsThis review provides dosing, safety, and efficacy information from Amgen-sponsored cinacalcet pediatric trials and data from non-Amgen sponsored clinical studies.ResultsThe Amgen cinacalcet pediatric clinical development program consisted of two Phase 3 randomized studies, one Phase 3 single arm extension study, one open-label Phase 2 study, and two open-label Phase 1 studies. Effects of cinacalcet on PTH varied across studies. Overall, 7.4 to 57.1% of subjects who received cinacalcet in an Amgen clinical trial attained PTH levels within recommended target ranges and 22.2 to 70.6% observed a ≥ 30% reduction in PTH. In addition, significant reductions in PTH were demonstrated in all non-Amgen-supported studies.ConclusionsTo help inform the pediatric nephrology community, this manuscript contains the most comprehensive review of cinacalcet usage in pediatric CKD patients to date.
Highlights
End-stage renal disease (ESRD) in children is rare with 18– 100 per million patients requiring renal replacement therapyElectronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.Dermatology, Femme Mère Enfant Hospital, Bron, France globally [1]
Secondary hyperparathyroidism is a compensatory complication of chronic kidney disease (CKD). sHPT is characterized by persistently elevated parathyroid hormone (PTH) concentrations in serum or plasma, and it represents an adaptive response that serves primarily to maintain calcium homeostasis systemically as kidney function declines [3]
Alterations in fibroblast growth factor 23 (FGF23), vitamin D metabolism, and calcium and phosphorus regulation lead to a reduction in signaling through the calcium-sensing receptor (CaSR) and an increase in PTH secretion, resulting in higher PTH concentrations
Summary
Secondary hyperparathyroidism (sHPT) is a compensatory complication of chronic kidney disease (CKD). SHPT is characterized by persistently elevated parathyroid hormone (PTH) concentrations in serum or plasma, and it represents an adaptive response that serves primarily to maintain calcium homeostasis systemically as kidney function declines [3]. Alterations in fibroblast growth factor 23 (FGF23), vitamin D metabolism, and calcium and phosphorus regulation lead to a reduction in signaling through the calcium-sensing receptor (CaSR) and an increase in PTH secretion, resulting in higher PTH concentrations. Late in the course of CKD, phosphorus retention and overt hyperphosphatemia, together with skeletal resistance to the calcemic action of PTH, can affect calcium metabolism adversely and further increase PTH secretion. Secondary hyperparathyroidism (sHPT), a complication of chronic kidney disease (CKD) characterized by persistently elevated parathyroid hormone (PTH), alterations in calcium-phosphorus homeostasis, and vitamin D metabolism, affects 50% of children receiving dialysis. The calcimimetic cinacalcet is approved for use in adults with sHPT on dialysis, but is not approved for pediatric use outside Europe
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
