Cinacalcet as rescue therapy for refractory hyperparathyroidism in young children with advanced chronic kidney disease

Aura J. Arenas Morales, Marissa J. DeFreitas, Chryso Katsoufis, Wacharee Seeherunvong, Jayanthi Chandar, Gaston E Zilleruelo, Michael Freundlich, Carolyn Abitbol

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1 Citation (Scopus)

Abstract

Background: 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. Methods: 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. Results: 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). Conclusions: 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.

Original languageEnglish (US)
JournalPediatric Nephrology
DOIs
StateAccepted/In press - Jan 1 2018

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Hyperparathyroidism
Chronic Renal Insufficiency
Parathyroid Hormone
Secondary Hyperparathyroidism
Growth
Therapeutics
Pediatrics
Cinacalcet Hydrochloride
Hypocalcemia
Bone Diseases
Vitamin D
Growth Hormone
Cardiovascular Diseases
Phosphates
Regression Analysis

Keywords

  • Calcimimetic
  • Cinacalcet
  • Growth
  • Hyperparathyroidism
  • Pediatric chronic kidney disease

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Nephrology

Cite this

@article{60ae80c77cdf43a1a85791a2ae68c5b1,
title = "Cinacalcet as rescue therapy for refractory hyperparathyroidism in young children with advanced chronic kidney disease",
abstract = "Background: 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. Methods: 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. Results: 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). Conclusions: 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.",
keywords = "Calcimimetic, Cinacalcet, Growth, Hyperparathyroidism, Pediatric chronic kidney disease",
author = "{Arenas Morales}, {Aura J.} and DeFreitas, {Marissa J.} and Chryso Katsoufis and Wacharee Seeherunvong and Jayanthi Chandar and Zilleruelo, {Gaston E} and Michael Freundlich and Carolyn Abitbol",
year = "2018",
month = "1",
day = "1",
doi = "10.1007/s00467-018-4055-7",
language = "English (US)",
journal = "Pediatric Nephrology",
issn = "0931-041X",
publisher = "Springer Verlag",

}

TY - JOUR

T1 - Cinacalcet as rescue therapy for refractory hyperparathyroidism in young children with advanced chronic kidney disease

AU - Arenas Morales, Aura J.

AU - DeFreitas, Marissa J.

AU - Katsoufis, Chryso

AU - Seeherunvong, Wacharee

AU - Chandar, Jayanthi

AU - Zilleruelo, Gaston E

AU - Freundlich, Michael

AU - Abitbol, Carolyn

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: 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. Methods: 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. Results: 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). Conclusions: 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.

AB - Background: 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. Methods: 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. Results: 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). Conclusions: 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.

KW - Calcimimetic

KW - Cinacalcet

KW - Growth

KW - Hyperparathyroidism

KW - Pediatric chronic kidney disease

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UR - http://www.scopus.com/inward/citedby.url?scp=85053490523&partnerID=8YFLogxK

U2 - 10.1007/s00467-018-4055-7

DO - 10.1007/s00467-018-4055-7

M3 - Article

C2 - 30203374

AN - SCOPUS:85053490523

JO - Pediatric Nephrology

JF - Pediatric Nephrology

SN - 0931-041X

ER -