Safety and Efficacy of Cinacalcet in Children Aged Under 3 Years on Maintenance Dialysis

Introduction: Secondary hyperparathyroidism (sHPT) is particularly severe in rapidly growing infants in dialysis. Although cinacalcet is effective and licensed in dialysis in children aged >3 years, its efficacy and safety for children aged <3 years is unknown. Methods: We identified 26 childr...

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Main Authors: Julie Bernardor, Sacha Flammier, Ilona Zagozdzon, Alexander D. Lalayiannis, Linda Koster-Kamphuis, Enrico Verrina, Eiske Dorresteijn, Isabella Guzzo, Dieter Haffner, Rukshana Shroff, Claus P. Schmitt, Justine Bacchetta
Format: Article
Language:English
Published: Elsevier 2024-07-01
Series:Kidney International Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2468024924016966
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author Julie Bernardor
Sacha Flammier
Ilona Zagozdzon
Alexander D. Lalayiannis
Linda Koster-Kamphuis
Enrico Verrina
Eiske Dorresteijn
Isabella Guzzo
Dieter Haffner
Rukshana Shroff
Claus P. Schmitt
Justine Bacchetta
author_facet Julie Bernardor
Sacha Flammier
Ilona Zagozdzon
Alexander D. Lalayiannis
Linda Koster-Kamphuis
Enrico Verrina
Eiske Dorresteijn
Isabella Guzzo
Dieter Haffner
Rukshana Shroff
Claus P. Schmitt
Justine Bacchetta
author_sort Julie Bernardor
collection DOAJ
description Introduction: Secondary hyperparathyroidism (sHPT) is particularly severe in rapidly growing infants in dialysis. Although cinacalcet is effective and licensed in dialysis in children aged >3 years, its efficacy and safety for children aged <3 years is unknown. Methods: We identified 26 children aged <3 years who were on dialysis and treated with cinacalcet between 2009 and 2021 in 8 European pediatric centers. Results: Median (interquartile range) age at the start of cinacalcet was 18 (interquartile range: 11–27) months, serum parathyroid hormone (PTH) was 792 (411–1397) pg/ml, corresponding to 11.6 (5.9–19.8) times the upper limit of normal (ULN). Serum calcium was 2.56 (2.43–2.75) mmol/l, and serum phosphate 1.47 (1.16–1.71) mmol/l. Serum 25-OH vitamin D (25–OHD) was 70 (60–89) nmol/l, 3 children were vitamin D deficient (<50 nmol/l). The initial cinacalcet dose was 0.4 (0.2–0.8) mg/kg/d and the maximum dose was 1.1 (0.6–1.2) mg/kg/d. The median follow-up under cinacalcet was 1.2 (0.7–2.0) years. PTH decreased to 4.3 (2.2–7.8) times the ULN after 6 months, to 2.0 (1.0–5.3) times ULN after 12 months, and to 1.6 (0.5–3.4) times thereafter (P = 0.017/0.003/<0.0001, log-transformed PTH). Seven of the 26 infants developed 10 hypocalcemic episodes <2.10 mmol/l. Oral calcium intake was 84% (66%–117%) of recommended nutrient intake at start, 100% (64%–142%) at 3 months and declined to 78% (65%–102%) at 12 months of therapy. Three children developed clinical signs of precocious puberty. Conclusion: Cinacalcet efficiently controlled severe sHPT in children aged <3 years and was associated with hypocalcemic episodes (similar to what is observed in older children) and precious puberty, thereby mandating meticulous control of calcium (considering nutrition, supplementation, and dialysate) and endocrine changes.
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spelling doaj-art-ffde01d002064a52a59b2be8a08b1d662025-08-20T03:45:08ZengElsevierKidney International Reports2468-02492024-07-01972096210910.1016/j.ekir.2024.04.061Safety and Efficacy of Cinacalcet in Children Aged Under 3 Years on Maintenance DialysisJulie Bernardor0Sacha Flammier1Ilona Zagozdzon2Alexander D. Lalayiannis3Linda Koster-Kamphuis4Enrico Verrina5Eiske Dorresteijn6Isabella Guzzo7Dieter Haffner8Rukshana Shroff9Claus P. Schmitt10Justine Bacchetta11Department of Pediatric Nephrology, Rheumatology and Dermatology, Reference Center for Rare Renal Diseases, Reference Center for Rare Diseases of Phosphate and Calcium, Femme Mère Enfant Hospital, Hospices Civils de Lyon, Lyon, France; INSERM 1033 Research Unit, Université Claude Bernard Lyon 1, Lyon, France; Department of Pediatric Nephrology, CHU de Nice, Hôpital Archet, Nice, France; Centre for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg, Germany; Correspondence: Julie Bernardor, Unité de Néphrologie Pédiatrique, Archet 2, CHU de Nice, 151 Route Saint-Antoine de Ginestière, 06200 Nice, France.Department of Pediatric Nephrology, Rheumatology and Dermatology, Reference Center for Rare Renal Diseases, Reference Center for Rare Diseases of Phosphate and Calcium, Femme Mère Enfant Hospital, Hospices Civils de Lyon, Lyon, FranceDepartment of Pediatrics, Nephrology and Hypertension, Medical University of Gdańsk, PolandPaediatric Nephrology, Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, UKDepartment of Pediatric Nephrology, University Medical Center, St. Radboud/Radboud University, Nijmegen, The NetherlandsDivision of Nephrology, Dialysis, and Transplantation, IRCCS Istituto Giannina Gaslini, Genova, ItalyDepartment of Pediatric Nephrology, Sophia Children’s Hospital, Erasmus Medical Center, Rotterdam, The NetherlandsDivision of Nephrology, Dialysis and Transplantation, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDepartment of Pediatric Kidney, Liver and Metabolic Diseases, Pediatric Research Center, Hannover Medical School, Hannover, GermanyPediatric Nephrology Unit, University College London Great Ormond Street Hospital for Children and Institute of Child Health, London, UKCentre for Pediatric and Adolescent Medicine, University Hospital Heidelberg, Im Neuenheimer Feld, Heidelberg, GermanyDepartment of Pediatric Nephrology, Rheumatology and Dermatology, Reference Center for Rare Renal Diseases, Reference Center for Rare Diseases of Phosphate and Calcium, Femme Mère Enfant Hospital, Hospices Civils de Lyon, Lyon, France; INSERM 1033 Research Unit, Université Claude Bernard Lyon 1, Lyon, FranceIntroduction: Secondary hyperparathyroidism (sHPT) is particularly severe in rapidly growing infants in dialysis. Although cinacalcet is effective and licensed in dialysis in children aged >3 years, its efficacy and safety for children aged <3 years is unknown. Methods: We identified 26 children aged <3 years who were on dialysis and treated with cinacalcet between 2009 and 2021 in 8 European pediatric centers. Results: Median (interquartile range) age at the start of cinacalcet was 18 (interquartile range: 11–27) months, serum parathyroid hormone (PTH) was 792 (411–1397) pg/ml, corresponding to 11.6 (5.9–19.8) times the upper limit of normal (ULN). Serum calcium was 2.56 (2.43–2.75) mmol/l, and serum phosphate 1.47 (1.16–1.71) mmol/l. Serum 25-OH vitamin D (25–OHD) was 70 (60–89) nmol/l, 3 children were vitamin D deficient (<50 nmol/l). The initial cinacalcet dose was 0.4 (0.2–0.8) mg/kg/d and the maximum dose was 1.1 (0.6–1.2) mg/kg/d. The median follow-up under cinacalcet was 1.2 (0.7–2.0) years. PTH decreased to 4.3 (2.2–7.8) times the ULN after 6 months, to 2.0 (1.0–5.3) times ULN after 12 months, and to 1.6 (0.5–3.4) times thereafter (P = 0.017/0.003/<0.0001, log-transformed PTH). Seven of the 26 infants developed 10 hypocalcemic episodes <2.10 mmol/l. Oral calcium intake was 84% (66%–117%) of recommended nutrient intake at start, 100% (64%–142%) at 3 months and declined to 78% (65%–102%) at 12 months of therapy. Three children developed clinical signs of precocious puberty. Conclusion: Cinacalcet efficiently controlled severe sHPT in children aged <3 years and was associated with hypocalcemic episodes (similar to what is observed in older children) and precious puberty, thereby mandating meticulous control of calcium (considering nutrition, supplementation, and dialysate) and endocrine changes.http://www.sciencedirect.com/science/article/pii/S2468024924016966cinacalcetinfantskidney failuresecondary hyperparathyroidism
spellingShingle Julie Bernardor
Sacha Flammier
Ilona Zagozdzon
Alexander D. Lalayiannis
Linda Koster-Kamphuis
Enrico Verrina
Eiske Dorresteijn
Isabella Guzzo
Dieter Haffner
Rukshana Shroff
Claus P. Schmitt
Justine Bacchetta
Safety and Efficacy of Cinacalcet in Children Aged Under 3 Years on Maintenance Dialysis
Kidney International Reports
cinacalcet
infants
kidney failure
secondary hyperparathyroidism
title Safety and Efficacy of Cinacalcet in Children Aged Under 3 Years on Maintenance Dialysis
title_full Safety and Efficacy of Cinacalcet in Children Aged Under 3 Years on Maintenance Dialysis
title_fullStr Safety and Efficacy of Cinacalcet in Children Aged Under 3 Years on Maintenance Dialysis
title_full_unstemmed Safety and Efficacy of Cinacalcet in Children Aged Under 3 Years on Maintenance Dialysis
title_short Safety and Efficacy of Cinacalcet in Children Aged Under 3 Years on Maintenance Dialysis
title_sort safety and efficacy of cinacalcet in children aged under 3 years on maintenance dialysis
topic cinacalcet
infants
kidney failure
secondary hyperparathyroidism
url http://www.sciencedirect.com/science/article/pii/S2468024924016966
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