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

Paweena Susantitaphong,Somratai Vadcharavivad,Teerada Susomboon,Wanchana Singhan,Netsiri Dumrongpisutikul,Ketsuda Jakchairoongruang,Somchai Eiam-Ong,Kearkiat Praditpornsilpa

doi:10.1080/0886022x.2018.1562356

Paweena Susantitaphong, Somratai Vadcharavivad + Show 6 more

Open Access

https://doi.org/10.1080/0886022x.2018.1562356

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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.

Highlights

Chronic kidney disease (CKD)-mineral bone disorder (MBD) develops as a systemic disorder of mineral and bone metabolism, including laboratory abnormalities such as parathyroid hormone (PTH), vitamin D, calcium, phosphate, fibroblast growth factor 23 (FGF-23), bone abnormalities, and vascular calcification [1]
All 45 participants were followed as a prospective cohort study for 24-week follow up and 12 weeks after discontinuing cinacalcet to further explore the effect on chronic kidney disease-mineral bone disorder (CKD-MBD) parameters including laboratory markers [calcium, phosphate, intact PTH (iPTH), FGF-23, bone alkaline phosphatase (BAP), vitamin D, 1,25 vitamin D, serum tartrate-resistant acid phosphatase 5 b (TRAP-5b), parathyroid gland size, and vascular calcification
At 3-week and 6-week follow up, the mean serum calcium was significantly decreased in the cinacalcet group, the dialysate calcium was increased, and there was a lowering trend of serum iPTH levels (Figures 1 and 2)

Summary

Introduction

Chronic kidney disease (CKD)-mineral bone disorder (MBD) develops as a systemic disorder of mineral and bone metabolism, including laboratory abnormalities such as parathyroid hormone (PTH), vitamin D, calcium, phosphate, fibroblast growth factor 23 (FGF-23), bone abnormalities, and vascular calcification [1]. The Kidney Disease Improving Global Outcomes (KDIGO) 2017 recommended that the patients with CKD stage 5D require PTH-lowering therapy including calcimimetics, calcitriol, and vitamin D analogs. 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. 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. 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

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Conclusion