Longitudinal changes in bone and mineral metabolism after cessation of cinacalcet in dialysis patients with secondary hyperparathyroidism

• Published in: BMC nephrology Vol. 19; no. 1; p. 113
• Main Authors: Ruderman, Irene, Smith, Edward R, Toussaint, Nigel D, Hewitson, Tim D, Holt, Stephen G
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 15.05.2018; BioMed Central; BMC
• Subjects: Aged; Aged, 80 and over; Biomarkers - blood; Bone Density - drug effects; Bone Density - physiology; Calcimimetic Agents - administration & dosage; Calciprotein particles; Calcium - blood; Chronic kidney failure; Cinacalcet; Cinacalcet - administration & dosage; Cohort Studies; Dialysis; Dosage and administration; Drug therapy; End-stage kidney disease; Female; Health aspects; Hemodialysis patients; Humans; Hyperparathyroidism; Hyperparathyroidism, Secondary - blood; Hyperparathyroidism, Secondary - diagnosis; Hyperparathyroidism, Secondary - therapy; Longitudinal Studies; Male; Middle Aged; Mineral metabolism; Parathyroid hormone; Parathyroid Hormone - blood; Prospective Studies; Renal Dialysis - adverse effects; Renal Dialysis - trends; Secondary hyperparathyroidism; Withholding Treatment - trends; Australia; End-stage kidney disease; Dialysis; Calciprotein particles; Cinacalcet; Parathyroid hormone; Secondary hyperparathyroidism
• ISSN: 1471-2369; 1471-2369
• DOI: 10.1186/s12882-018-0910-9

The calcimimetic agent cinacalcet is effective for the management of secondary hyperparathyroidism (SHPT) in dialysis patients. Changes to reimbursement of cinacalcet in Australia provided an opportunity to assess effects of medication cessation on biochemical and clinical outcomes in dialysis patients, including changes to novel biomarkers such as calciprotein particles (CPP). CPP are nanoparticles of mineral and protein in the circulation associated with increased vascular calcification in patients with chronic kidney disease. Dialysis patients from a single center who ceased cinacalcet between August 2015 and March 2016 were included in a prospective observational study. Bloods were taken at the time of cessation of cinacalcet and at 1, 6 and 12 months. Clinical and biochemical outcomes were compared with an age- and gender-matched cohort of cinacalcet-naïve dialysis patients. Sixty-two patients participated in the study. Mean age was 69.6 ± 13.2 years. Biochemical changes over 12 months following cessation of cinacalcet included an increase in serum parathyroid hormone (PTH) (42.2 [IQR 27.8-94.6] pmol/L to 114.8 [83.9-159.1] pmol/L [p < 0.001]), serum calcium (2.31 ± 0.21 mmol/L to 2.46 ± 0.14 mmol/L [p < 0.001]) and primary CPP (CPP-I) (p = 0.002). Changes in CPP were associated with an increase in PTH (p = 0.007), calcium (p = 0.002) and ferritin (p = 0.02) but a reduction in serum albumin (p = 0.001). Over the 12-month period, there were two fractures, five cardiovascular events, one episode of calciphylaxis, and one parathyroidectomy, with a mortality rate of 19% (n = 13). Uniquely we report the effects of cinacalcet withdrawal in a real world setting with demonstrated increases in PTH, serum calcium and CPP subsets, novel CKD-MBD related factors, over a 12-month period.