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Randomized trial of two maintenance doses of vitamin D in children with chronic kidney disease

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Abstract

Background

Correction of nutritional vitamin deficiency is recommended in children with chronic kidney disease (CKD). The optimal daily dose of vitamin D to achieve or maintain vitamin D sufficiency is unknown.

Methods

We conducted a phase III, double-blind, randomized trial of two doses of vitamin D3 in children ≥ 9 years of age with CKD stages 3–5 or kidney transplant recipients. Patients were randomized to 1000 IU or 4000 IU of daily vitamin D3 orally. We measured 25-hydroxvitamin D (25(OH)D) levels at baseline, 3 months and 6 months. The primary efficacy outcome was the percentage of patients who were vitamin D replete (25(OH)D ≥ 30 ng/mL) at 6 months.

Results

Ninety-eight patients were enrolled: 49 randomized into each group. Eighty (81.6%) patients completed the study and were analyzed. Baseline plasma 25(OH)D levels were ≥ 30 ng/mL in 12 (35.3%) and 12 (27.3%) patients in the 1000 IU and 4000 IU treatment groups, respectively. At 6 months, plasma 25(OH)D levels were ≥ 30 ng/mL in 33.3% (95% CI: 18.0–51.8%) and 74.4% (95% CI: 58.8–86.5%) in the 1000 IU and 4000 IU treatment groups, respectively (p = 0.0008). None of the patients developed vitamin D toxicity or hypercalcemia.

Conclusions

In children with CKD, 1000 IU of daily vitamin D3 is unlikely to achieve or maintain a plasma 25(OH)D ≥ 30 ng/mL. In children with CKD stages 3–5, a dose of vitamin D3 4000 IU daily was effective in achieving or maintaining vitamin D sufficiency.

Clinical Trial Registration: ClinicalTrials.gov identifier: NCT01909115

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Data availability

De-identified individual participant data (including data dictionaries) will be made available, in addition to study protocols, the statistical analysis plan, and the informed consent form. The data will be made available upon publication to researchers who provide a methodologically sound proposal for use in achieving the goals of the approved proposal. The data will be available up to 3 years following article publication. Proposals should be submitted to Larry Greenbaum, MD at lgreen6@emory.edu.

Code availability

Not applicable.

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Acknowledgements

The Pediatric Research Alliance Biostatistics Core of Emory University and Children’s Healthcare of Atlanta provided biostatistical support. This study was funded by the Friends Fund of Children’s Healthcare of Atlanta. We would also like to thank Priscilla Quach and Margaret Kamel for patient enrollment and research guidance, respectively.

Funding

This study was funded by Friends Grant, Children’s Healthcare of Atlanta.

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Texas Southwestern Medical Center, 1935 Medical District Drive, Dallas, TX, USA

    Shahid Nadeem

  2. Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA

    Vin Tangpricha

  3. Division of Endocrinology, Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, Emory University, Atlanta, GA, USA

    Thomas R. Ziegler

  4. Investigational Drug Service Pharmacy, Children’s Healthcare of Atlanta, Atlanta, GA, USA

    James E. Rhodes

  5. Rollins School of Public Health, Emory University, Atlanta, GA, USA

    Traci Leong

  6. Department of Pediatrics, Emory University, Atlanta, GA, USA

    Yijin Xiang

  7. Division of Pediatric Nephrology, Department of Pediatrics, Emory University and Children’s Healthcare of Atlanta, Atlanta, GA, USA

    Larry A. Greenbaum

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  1. Shahid Nadeem
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  2. Vin Tangpricha
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  3. Thomas R. Ziegler
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Contributions

Dr. Nadeem conceptualized and designed the study, drafted the initial manuscript, and reviewed and revised the manuscript.

Drs. Tangpricha and Ziegler provided guidance in the study design, and provided critical review of the manuscript.

James Rhodes performed patient randomization, administered vitamin D medication, and performed critical review of the manuscript.

Dr. Traci Leong and Yijin Xiang organized the data, performed data analysis and provided critical review of the manuscript.

Dr. Greenbaum conceptualized and designed the study, performed data analysis, partially drafted the manuscript and provided critical review of the manuscript.

Corresponding author

Correspondence to Shahid Nadeem.

Ethics declarations

Ethics approval

Approval was obtained from the ethics committee of Emory University and Children’s Healthcare of Atlanta. The procedures used in this study adhere to the tenets of the Declaration of Helsinki.

Consent to participate

Informed consent was obtained from legal guardians and assent from participants when applicable.

Consent for publication

All authors approved the manuscript as submitted and agree to be accountable for all aspects of the work.

Competing interests

The authors declare no competing interests.

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Nadeem, S., Tangpricha, V., Ziegler, T.R. et al. Randomized trial of two maintenance doses of vitamin D in children with chronic kidney disease. Pediatr Nephrol 37, 415–422 (2022). https://doi.org/10.1007/s00467-021-05228-z

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  • DOI: https://doi.org/10.1007/s00467-021-05228-z

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