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Vitamin D supplementation in children and young adults with persistent proteinuria secondary to glomerular disease

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Abstract

Background

Vitamin D deficiency is common in glomerular disease. Supplementation may be ineffective due to ongoing urinary losses of vitamin D binding protein. We sought to determine if daily cholecalciferol supplementation would increase vitamin D concentrations in children with glomerular disease and persistent proteinuria, without adverse effects.

Methods

Eighteen participants at least 5 years of age with primary glomerular disease and urine protein:creatinine ratio ≥ 0.5 were enrolled from four pediatric nephrology practices to receive cholecalciferol supplementation: 4,000 IU or 2,000 IU per day for serum 25 hydroxyvitamin vitamin D (25OHD) concentrations < 20 ng/mL and 20 ng/mL to < 30 ng/mL, respectively. Measures of vitamin D and mineral metabolism were obtained at baseline and weeks 6 and 12. Multivariable generalized estimating equation (GEE) regression estimated mean percent changes in serum 25OHD concentration.

Results

Median baseline 25OHD was 12.8 ng/mL (IQR 9.3, 18.9) and increased to 27.8 ng/mL (20.5, 36.0) at week 6 (p < 0.001) without further significant increase at week 12. A total of 31% of participants had a level ≥ 30 ng/mL at week 12. Supplementation was stopped in two participants at week 6 for mildly elevated calcium and phosphorus, respectively, with subsequent declines in 25OHD of > 20 ng/mL. In the adjusted GEE model, 25OHD was 102% (95% CI: 64, 141) and 96% (95% CI: 51, 140) higher versus baseline at weeks 6 and 12, respectively (p < 0.001).

Conclusion

Cholecalciferol supplementation in vitamin D deficient children with glomerular disease and persistent proteinuria safely increases 25OHD concentration. Ideal dosing to fully replete 25OHD concentrations in this population remains unknown.

Clinical trial

NCT01835639.

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Acknowledgements

The authors would like to thank Amy York, PA, and Maryjane Benton, RN, BSN, for their assistance with study coordination and project management.

Funding

This work was supported by K23 DK093556 and the Nephcure Foundation-American Society of Nephrology Research Grant (PI: Michelle Denburg). Statistical analysis was supported by The Children’s Hospital of Philadelphia Pediatric Center of Excellence in Nephrology (P50 DK114786). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health, Nephcure Foundation or the American Society of Nephrology.

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Authors and Affiliations

  1. Division of Nephrology, Department of Pediatrics, The Children’s Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Pennsylvania, PA, USA

    Amy J. Kogon, Natalie Walker & Michelle R. Denburg

  2. Biostatistics and Data Management Core, The Children’s Hospital of Philadelphia, Pennsylvania, PA, USA

    Lance S. Ballester

  3. Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania and The Children’s Hospital of Philadelphia, Pennsylvania, PA, USA

    Jarcy Zee & Michelle R. Denburg

  4. Division of Pediatric Nephrology, Department of Pediatrics, Nemours/Alfred I. duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE, USA

    Joshua J. Zaritsky

  5. Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Meredith A. Atkinson

  6. Cohen Children’s Medical Center of NY, New Hyde Park, New York, USA

    Christine B. Sethna

  7. Departments of Laboratory Medicine and Medicine, Kidney Research Institute, University of Washington, Seattle, DC, USA

    Andrew N. Hoofnagle

  8. Department of Pediatrics, Stanford School of Medicine, Palo Alto, CA, USA

    Mary B. Leonard

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  1. Amy J. Kogon
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  2. Lance S. Ballester
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  3. Jarcy Zee
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  4. Natalie Walker
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  10. Michelle R. Denburg
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Contributions

Michelle R. Denburg and Mary B. Leonard took part in conceptualization; Michelle R. Denburg, Mary B. Leonard, Andrew N. Hoofnagle involved in methodology; Amy J. Kogon, Lance Ballester, Natalie Walker, Michelle R. Denburg involved in formal analysis and investigation; Amy J Kogon, Lance Ballester, Michelle R. Denburg took part in writing—original draft preparation; Amy J. Kogon, Lance Ballester, Natalie Walker, Joshua Zaritsky, Meredith Atkinson, Christine B Sethana, Andrew N Hoofnagle, Mary B Leonard, Michelle R Denburg involved in writing—review and editing; Michelle R. Denburg took part in funding acquisition; Michelle R. Denburg and Andrew R. Hoofnagle took part in resources; Michelle R. Denburg and Mary B Leonard took part in supervision.

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Correspondence to Amy J. Kogon.

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Kogon, A.J., Ballester, L.S., Zee, J. et al. Vitamin D supplementation in children and young adults with persistent proteinuria secondary to glomerular disease. Pediatr Nephrol 38, 749–756 (2023). https://doi.org/10.1007/s00467-022-05660-9

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