Pediatric Nephrology

, Volume 34, Issue 1, pp 129–135 | Cite as

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

  • Aura J. Arenas Morales
  • Marissa J. DeFreitas
  • Chryso P. Katsoufis
  • Wacharee Seeherunvong
  • Jayanthi Chandar
  • Gaston Zilleruelo
  • Michael Freundlich
  • Carolyn L. AbitbolEmail author
Original Article



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.


Hyperparathyroidism 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.

Funding information

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.


  1. 1.
    Kramer A, Stel VS, Tizard J, Verrina E, Rönnholm K, Pálsson R, Maxwell H, Jager KJ (2009) Characteristics and survival of young adults who started renal replacement therapy during childhood. Nephrol Dial Transplant 24:926–933CrossRefGoogle Scholar
  2. 2.
    Mitsnefes MM, Laskin BL, Dahhou M, Zhang X, Foster BJ (2013) Mortality risk among children initially treated with dialysis for end-stage kidney disease, 1990–2010. JAMA 309:1921–1929CrossRefGoogle Scholar
  3. 3.
    Furth SL, Stablein D, Fine RN, Powe NR, Fivush BA (2002) Adverse clinical outcomes associated with short stature at dialysis initiation: a report of the North American pediatric renal transplant Cooperative study. Pediatrics 109:909–913CrossRefGoogle Scholar
  4. 4.
    Webb NJA, Lerner G, Warady BA, Dell KM, Greenbaum LA, Ariceta G, Hoppe B, Linde P, Lee HJ, Eldred A, Dufek MB (2017) Efficacy and safety of paricalcitol in children with stages 3 to 5 chronic kidney disease. Pediatr Nephrol 32(7):1221–1232CrossRefGoogle Scholar
  5. 5.
    Freundlich M, Abitbol CL (2017) Oral paricalcitol: expanding therapeutic options for pediatric chronic kidney disease patients. Pediatr Nephrol 32(7):1103–1108CrossRefGoogle Scholar
  6. 6.
    KDIGO (2017) Clinical practice guideline update for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kidney Int Suppl 7:1–59CrossRefGoogle Scholar
  7. 7.
    Schlieper G, Floege J (2008) Calcimimetics in CKD-results from recent clinical studies. Pediatr Nephrol 23(10):1721–1728CrossRefGoogle Scholar
  8. 8.
    Silverstein DM, Kher KK, Moudgil A, Khurana M, Wilcox J, Moylan K (2008) Cinacalcet is efficacious in paediatric dialysis patients. Pediatr Nephrol 23:1817–1822CrossRefGoogle Scholar
  9. 9.
    Muscheites J, Wigger M, Drueckler E, Fischer DC, Kundt G, Haffner D (2008) Cinacalcet for secondary hyperparathyroidism in children with end-stage renal disease. Pediatr Nephrol 23(10):1823–1829CrossRefGoogle Scholar
  10. 10.
    Wu S, Palese T, Mishra OP, Delivoria-Papadopoulos M, De Luca F (2004) Effects of Ca2+ sensing receptor activation in the growth plate. FASEB J 18(1):143–145CrossRefGoogle Scholar
  11. 11.
    Nakagawa K, Pérez EC, Oh J, Santos F, Geldyyev A, Gross ML, Schaefer F, Schmitt CP (2008) Cinacalcet does not affect longitudinal growth but increases body weight gain in experimental uraemia. Nephrol Dial Transplant 23:2761–2767CrossRefGoogle Scholar
  12. 12.
    Edney A (2013) Amgen pediatric trials of Sensipar halted by FDA after death. Businessweek Accessed 11 Dec 2017
  13. 13.
    Srivastava T, Jafri S, Truog WE, Sebestyen VanSickle J, Manimtim WM, Alon US (2017) Successful reversal of furosemide-induced secondary hyperparathyroidism with cinacalcet. Pediatrics CrossRefGoogle Scholar
  14. 14.
    Srivastava T, Krudys J, Mardis NJ, Sebestyen-VanSickle J, Alon US (2016) Cinacalcet as adjunctive therapy in pseudohypoparathyroidism type 1b. Pediatr Nephrol 31(5):795–800CrossRefGoogle Scholar
  15. 15.
    Srivastava T, Alon US (2013) Cinacalcet as adjunctive therapy for hereditary 1,25-dihydroxyvitamin D-resistant rickets. J Bone Miner Res 28(5):992–996CrossRefGoogle Scholar
  16. 16.
    Alon US, VandeVoorde RG (2010) Beneficial effect of cinacalcet in a child with familial hypocalciuric hypercalcemia. Pediatr Nephrol 25(9):1747–1750CrossRefGoogle Scholar
  17. 17.
    Alon US, Levy-Olomucki R, Moore WV, Stubbs J, Liu S, Quarles LD (2008) Calcimimetics as an adjuvant treatment for familial hypophosphatemic rickets. Clin J Am Soc Nephrol 3(3):658–664CrossRefGoogle Scholar
  18. 18.
    National Kidney Foundation (2005) K/DOQI clinical practice guidelines for bone metabolism and disease in children with chronic kidney disease. Am J Kidney Dis 46(S1):1–121Google Scholar
  19. 19.
    National Center for Health Statistics: Centers for Disease Control and World health Organization growth charts:
  20. 20.
    Parfrey PS, Chertow GM, Block GA, Correa-Rotter R, Drüeke TB, Floege J, Herzog CA, London GM, Mahaffey KW, Moe SM, Wheeler DC, Dehmel B, Trotman ML, Modafferi DM, Goodman WG (2013) The clinical course of treated hyperparathyroidism among patients receiving hemodialysis and the effect of cinacalcet: the EVOLVE trial. J Clin Endocrinol Metab 98(12):4834–4844CrossRefGoogle Scholar
  21. 21.
    Platt C, Inward C, McGraw M, Dudley J, Tizard J, Burren C, Saleem MA (2010) Middle-term use of Cinacalcet in paediatric dialysis patients. Pediatr Nephrol 25:143–148CrossRefGoogle Scholar
  22. 22.
    Alharthi AA, Kamal NM, Abukhatwah MW, Sherief LM (2015) Cinacalcet in pediatric and adolescent chronic kidney disease: a single-center experience. Medicine 94(2):e4012CrossRefGoogle Scholar
  23. 23.
    Rees L (2008) What parathyroid hormone levels should we aim for in children with stage 5 chronic kidney disease; what is the evidence? Pediatr Nephrol 23:179–184CrossRefGoogle Scholar
  24. 24.
    Haffner D, Schaefer F (2013) Searching the optimal PTH target range in children undergoing peritoneal dialysis: new insights from international cohort studies. Pediatr Nephrol 28:537–545CrossRefGoogle Scholar
  25. 25.
    Salusky IB, Ramirez JA, Oppenheim W, Gales B, Segre GV, Goodman WG (1994) Biochemical markers of renal osteodystrophy in pediatric patients undergoing CAPD/CCPD. Kidney Int 45:253–258CrossRefGoogle Scholar
  26. 26.
    Goodman WG, Ramirez JA, Belin TR, Chon Y, Gales B, Segre GV, Salusky IB (1994) Development of adynamic bone in patients with secondary hyperparathyroidism after intermittent calcitriol therapy. Kidney Int 46:1160–1166CrossRefGoogle Scholar

Copyright information

© IPNA 2018

Authors and Affiliations

  • Aura J. Arenas Morales
    • 1
  • Marissa J. DeFreitas
    • 1
  • Chryso P. Katsoufis
    • 1
  • Wacharee Seeherunvong
    • 1
  • Jayanthi Chandar
    • 1
  • Gaston Zilleruelo
    • 1
  • Michael Freundlich
    • 1
  • Carolyn L. Abitbol
    • 1
    Email author
  1. 1.Division of Pediatric Nephrology, Holtz Children’s HospitalUniversity of MiamiMiamiUSA

Personalised recommendations