Cinacalcet as rescue therapy for refractory hyperparathyroidism in young children with advanced chronic kidney disease
Studies in the use of the calcimimetic, cinacalcet, in pediatric chronic kidney disease (CKD) are few and limited to older children with secondary hyperparathyroidism (sHPT), a major morbid complication contributing to poor growth, bone deformities, and cardiovascular disease. Our objectives were to determine a safe and effective dosing regimen of cinacalcet in the treatment of infants and young children with sHPT that was refractory to standard care and to examine their growth during treatment.
Ten young pediatric patients with advanced CKD were studied retrospectively during 11 courses of treatment with cinacalcet. All had severe sHPT with intact parathyroid hormone (iPTH) levels ≥ 500 pg/ml and were refractory to standard therapy with phosphate binders and active vitamin D analogs at high doses for > 30 days. The cinacalcet dose was advanced by 50% every 2–4 weeks to achieve a decline in the iPTH to a goal of 150–300 pg/ml. Linear growth was assessed at 6-month intervals by change in z-scores (△SDS) for length before and during cinacalcet therapy.
Median age at initiation of cinacalcet was 18 months (IQR 6, 36) with an average starting dose of 0.7 ± 0.2 mg/kg/day. Median effective dose required to reach iPTH goal of 150–300 pg/ml was 2.8 mg/kg/day (IQR 2.0, 3.1), and time to goal was 112 days (IQR 56, 259) with a median overall decline in iPTH of 82% from baseline by 6 months (p < 0.0001). No subject experienced a clinical adverse event, although 4 had biochemical asymptomatic hypocalcemia. Linear growth improved significantly during cinacalcet therapy (△SDS − 0.62 ± 1.2 versus + 0.91 ± 1.4; p < 0.005). By multiple regression analysis, the primary determinants of growth were concurrent treatment with growth hormone and age < 2 years (R2 = 89.6%; p < 0.001). A shorter treatment time required to achieve iPTH goals also was associated with improved growth (r = − 0.75; p < 0.01).
Cinacalcet may be used effectively and safely in infants and small children with refractory sHPT in advanced CKD using a cautious dosing regimen. Cinacalcet successfully brings iPTH to target level and supports growth when other treatments have been ineffective.
KeywordsHyperparathyroidism Pediatric chronic kidney disease Calcimimetic Cinacalcet Growth
We would like to thank Dr. Gabriel Contreras, Professor of Medicine, Division of Nephrology and Hypertension, for his service in the scholarly review of this manuscript.
This work was supported in part by a grant from the Florida Department of Health Children’s Medical Services and the 2015 Micah Batchelor Children’s Research Award.
Compliance with ethical standards
The study was approved by the University of Miami Institutional Review Board. Patient confidentiality was protected in compliance with the HIPAA (Health Insurance Portability & Accountability Act).
Conflict of interest
The authors declare that they have no conflict of interest.
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