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Calcifediol supplementation in adults on hemodialysis: a randomized controlled trial

Journal of Nephrology volume 35, pages 517–525 (2022)Cite this article

Abstract

Background

Vitamin D deficiency is associated with increased risks of mortality in people with chronic kidney disease. The benefits and harm of vitamin D supplementation on cardiovascular outcomes and mortality are unknown. We aimed to assess the effectiveness of calcifediol in reducing mortality in patients with vitamin D insufficiency on hemodialysis compared to no additional therapy.

Methods

A phase III, multicenter, randomized, open-label trial was conducted including 284 adults with vitamin D insufficiency undergoing hemodialysis who were randomly assigned to receive oral calcifediol or standard care for 24 months.

Results

Two hundred eighty-four participants were enrolled (143 assigned to the calcifediol group and 141 to the no additional therapy group). The primary outcome (mortality) occurred in 34 and 31 participants in the calcifediol and control group, respectively [hazard ratio (HR) 1.03; 95% confidence interval (CI) 0.63–1.67]. Calcifediol had no detectable effects on cardiovascular death (HR 1.06; 95% CI 0.41–2.74), non-cardiovascular death (HR 1.13; 95% CI 0.62–2.04), nonfatal myocardial infarction (HR 0.20; 95% CI 0.02–1.67) or nonfatal stroke (HR could not be estimated). The incidence of hypercalcemia and hyperphosphatemia was similar between groups. None of the participants underwent parathyroidectomy.

Conclusions

In adults treated with hemodialysis and who had vitamin D insufficiency, calcifediol supplementation for 24 months had inconclusive effects on mortality and cardiovascular outcomes.

Trial registration number

NCT01457001

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Data availability statement

The datasets generated and/or analyzed during the current study are available from the corresponding author on reasonable request. Authors confirmed that the results presented in this paper have not been published previously in whole or part, except in abstract format.

Code availability

Not applicable.

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Acknowledgements

We acknowledge Dr. Boris Biclow for his support with the statistical analyses.

Mineral Metabolism Study Group of the Italian Society of Nephrology: Carlo Massimetti, Fabio Pennacchiotti, Antonio Mannarino, Cristina Grimaldi, Vincenzo Savica, Onofrio Schillaci, Olga Credentino, Maria Domenica Casu, Carlo Lomonte, Valentina Vigo, Giuseppe Grandaliano, Stefano Netti, Filippo Aucella, Massimo Morosetti, Roberto Boero, Francesco Soleti, Efstratios Fasianos, Maria Polidoro, Domenico Santoro, Alessandra Perna, Fabio Malberti, Ludovica d'Apice, Romano Musacchio, Maria Carla Porcu, Giuseppe Cianciolo, Silverio Rotondi e Maria Luisa Muci.

Funding

This work was a no-profit trial supported by the Italian Society of Nephrology. Grant/award number: not applicable.

Author information

Authors and Affiliations

  1. Struttura complessa di nefrologia e dialisi ASL Taranto, Taranto, Italy

    Luigi Morrone

  2. Department of Medicine, University of Otago, Christchurch, New Zealand

    Suetonia C. Palmer

  3. Faculty of Medicine and Health, Sydney School of Public Health, University of Sydney, Sydney, Australia

    Valeria M. Saglimbene, Patrizia Natale & Giovanni F. M. Strippoli

  4. Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Bergamo, Italy

    Annalisa Perna

  5. Nephrology Dialysis and Kidney Transplantation Unit, IRCCS, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

    Giuseppe Cianciolo

  6. Unit of Nephrology and Hypertension, Department of Public Health, University of Naples Federico II, Naples, Italy

    Domenico Russo

  7. Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy

    Loreto Gesualdo, Patrizia Natale & Giovanni F. M. Strippoli

  8. Scuola di Specializzazione in Nefrologia, Policlinico S. Orsola-Malpighi, Università degli Studi di Bologna, Bologna, Italy

    Antonio Santoro

  9. Dipartimento di Nefrologia, Policlinico Umberto I, Università La Sapienza di Roma, Roma, Italy

    Sandro Mazzaferro

  10. Struttura Complessa di Nefrologia e Dialisi ASST Santi Paolo e Carlo, Dipartimento di Scienze della Salute, Università di Milano, Milano, Italy

    Mario Cozzolino

  11. Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy

    Adamasco Cupisti

  12. Struttura Complessa di Nefrologia e Dialisi, A.O. Ospedali Riuniti Marche Nord, Pesaro, Italy

    Marina Di Luca

  13. Struttura Complessa di Nefrologia e Dialisi, A.O. “San Giuseppe Moscati”, Avellino, Italy

    Biagio Di Iorio

Authors
  1. Luigi Morrone
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  2. Suetonia C. Palmer
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  3. Valeria M. Saglimbene
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  4. Annalisa Perna
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  5. Giuseppe Cianciolo
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  6. Domenico Russo
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  7. Loreto Gesualdo
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  8. Patrizia Natale
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  9. Antonio Santoro
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  10. Sandro Mazzaferro
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  11. Mario Cozzolino
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  12. Adamasco Cupisti
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  13. Marina Di Luca
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  14. Biagio Di Iorio
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  15. Giovanni F. M. Strippoli
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Consortia

the Mineral Metabolism Study Group of the Italian Society of Nephrology

  • Carlo Massimetti
  • , Fabio Pennacchiotti
  • , Antonio Mannarino
  • , Cristina Grimaldi
  • , Vincenzo Savica
  • , Onofrio Schillaci
  • , Olga Credentino
  • , Maria Domenica Casu
  • , Carlo Lomonte
  • , Valentina Vigo
  • , Giuseppe Grandaliano
  • , Stefano Netti
  • , Filippo Aucella
  • , Massimo Morosetti
  • , Roberto Boero
  • , Francesco Soleti
  • , Efstratios Fasianos
  • , Maria Polidoro
  • , Domenico Santoro
  • , Alessandra Perna
  • , Fabio Malberti
  • , Ludovica d’Apice
  • , Romano Musacchio
  • , Maria Carla Porcu
  • , Giuseppe Cianciolo
  • , Silverio Rotondi
  •  & Maria Luisa Muci

Contributions

Conception and design: LM, GS; data acquisition: LM, GC, AC, BDI, MDL, SM, AP; data analysis: AP; data interpretation: LM, SP, VS, AP, GS. Each author contributed important intellectual content during manuscript drafting or revision, accepts personal accountability for the author’s own contributions, and agrees to ensure that questions pertaining to the accuracy or integrity of any portion of the work are appropriately investigated and resolved.

Corresponding author

Correspondence to Giovanni F. M. Strippoli.

Ethics declarations

Conflict of interest

The authors have no relevant financial or non-financial interests to disclose.

Ethical approval

This study was performed in line with the principles of the Declaration of Helsinki. The study received Institutional Review Board approval from the Ethics Committee of the “Azienda Ospedaliera G. Rummo” of Benevento (deliberation n. 294, 13/04/2012).

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent for publication

Not applicable.

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The members of the Mineral Metabolism Study Group of the Italian Society of Nephrology are listed in Acknowledgements.

Supplementary Information

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Morrone, L., Palmer, S.C., Saglimbene, V.M. et al. Calcifediol supplementation in adults on hemodialysis: a randomized controlled trial. J Nephrol 35, 517–525 (2022). https://doi.org/10.1007/s40620-021-01104-z

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  • DOI: https://doi.org/10.1007/s40620-021-01104-z

Keywords

  • Calcifediol
  • Vitamin D
  • Hemodialysis
  • ESKD
  • Mortality

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