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The use of cinacalcet after pediatric renal transplantation: an international CERTAIN Registry analysis

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Abstract

Background

Secondary hyperparathyroidism (SHPT) may persist after renal transplantation (RTx), inducing hypophosphatemia and hypercalcemia that precludes the use of vitamin D analogs. The calcimimetic cinacalcet improved plasma calcium and parathyroid hormone (PTH) levels in randomized controlled trials in adults after RTx, but pediatric data are scarce.

Methods

In this retrospective study, we analyzed 20 pediatric patients from the Cooperative European Paediatric Renal TransplAnt Initiative (CERTAIN) Registry who received cinacalcet after RTx. The results are presented as median and interquartile range (25th–75th percentile).

Results

At 13.7 (11.0–16.5) years of age, 20 pediatric patients received a renal allograft. Cinacalcet was introduced at 0.4 (0.3–2.7) years post-transplant at an estimated glomerular filtration rate (eGFR) of 50 (34–66) mL/min/1.73 m2, plasma calcium of 2.58 (2.39–2.71) mmol/L, age-standardized (z score) phosphate of − 1.7 (− 2.7−− 0.4), and PTH of 136 (95–236) ng/L. The starting dose of cinacalcet was 0.5 (0.3–0.8) mg/kg per day, with a maximum dose of 1.1 (0.5–1.3) mg/kg per day. With a follow-up of 3.0 (1.5–3.6) years on cinacalcet therapy, eGFR remained stable; PTH levels decreased to 66 (56–124) ng/L at the last follow-up (p = 0.015). One patient displayed hypocalcemia (1.8 mmol/L). Cinacalcet was withdrawn in three patients (hypocalcemia, parathyroidectomy, incompliance). Nephrocalcinosis of the graft was not reported.

Conclusions

This pilot study suggests that cinacalcet as off-label therapy for SHPT after pediatric RTx is efficacious in controlling post-transplant SHPT with acceptable tolerability. Continuing cinacalcet even with normal PTH can lead to dangerous life-threatening hypocalcemia. Therefore, at each subsequent visit, the need to continue cinacalcet must be assessed.

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Conflict of interest

Justine Bacchetta has been an investigator for the Amgen-sponsored trials on the use of cinacalcet in pediatric dialysis. Justine Bacchetta is the coordinator of the Amgen-sponsored international registry on the use of cinacalcet in pediatric dialysis, and the national principal investigator for the Amgen-sponsored trial on the use of etelcalcetide in pediatric dialysis. She received a research grant for experimental studies by Amgen.

Claus Peter Schmitt received financial support from Amgen for investigator-initiated experimental research, a travel grant, and is national principal investigator for the Amgen-sponsored trial on the use of etelcalcetide in pediatric dialysis.

No other relevant conflicts of interest are reported.

Funding

The authors received financial support from the CERTAIN Registry by a grant from the Dietmar Hopp Stiftung, the European Society for Paediatric Nephrology (ESPN), and the German Society for Paediatric Nephrology (GPN), and by grants from the pharmaceutical companies Astellas and Novartis.

The non-profit pediatric association of CHU de Nice (ADHPUN) paid for statistical analyses, performed by SARL Green Grow Scientific.

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Authors and Affiliations

  1. Reference Center for Rare Renal Disorders, Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Department of Pediatric Nephrology, Rheumatology and Dermatology, Femme Mère Enfant Hospital, Bron Cedex, France

    Julie Bernardor, Anne-Laure Sellier-Leclerc & Justine Bacchetta

  2. Department of Pediatric Nephrology, CHU de Nice, Hôpital Archet, 151 Route Saint-Antoine de Ginestière, 06200, Nice, France

    Julie Bernardor

  3. Department of Pediatrics I, University Children’s Hospital, Im Neuenheimer Feld 430, 69120, Heidelberg, Germany

    Claus Peter Schmitt, Kai Krupka & Burkhard Tönshoff

  4. University Medical Center, Hamburg, Germany

    Jun Oh

  5. Pediatric Nephrology, Pediatrics II, University Children’s Hospital Essen, Hufelandstrasse 55, 45122, Essen, Germany

    Anja Büscher

  6. Pediatric Nephrology and Renal Transplant Unit, Bambino Gesù Children’s Hospital-IRCCS, Piazza S. Onofrio 4, 00165, Rome, Italy

    Luca Dello Strologo

  7. Pediatric Nephrology Department, Faculty of Medicine, Ondokuz Mayis University, Samsun, Turkey

    Gurkan Genc

  8. University Children’s Hospital-Pediatric Nephrology, Jena, Germany

    Ulrike John

  9. Pediatric Nephrology, University Children’s Hospital Zurich, Zurich, Switzerland

    Marcus Weitz

  10. Pediatric Nephrology, University Children’s Hospital, Hoppe-Seyler-Str. 1, 72076, Tübingen, Germany

    Matthias Zirngibl

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  1. Julie Bernardor
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Correspondence to Julie Bernardor.

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For research purposes, an analysis of the multinational dataset requires approval of the predefined study protocol by the CERTAIN Registry Steering Committee. Written informed consent was obtained from all parents/guardians to participate in the registry, with assent from patients as appropriate for their age. The CERTAIN Registry has been approved by the ethics committee of each contributing center and is kept in full accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines.

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Bernardor, J., Schmitt, C.P., Oh, J. et al. The use of cinacalcet after pediatric renal transplantation: an international CERTAIN Registry analysis. Pediatr Nephrol 35, 1707–1718 (2020). https://doi.org/10.1007/s00467-020-04558-8

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