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Expression of vitamin D receptor, CYP27B1 and CYP24A1 hydroxylases and 1,25-dihydroxyvitamin D3 levels in stone formers

  • Thalita Lima Melo
  • Priscila Ligeiro Gonçalves Esper
  • Lysien Ivania Zambrano
  • Milene Subtil Ormanji
  • Fernanda Guedes Rodrigues
  • Ita Pfeferman HeilbergEmail author
Original Paper
  • 38 Downloads

Abstract

The expression of vitamin D receptor (VDR) and 1,25-dihydroxyvitamin D3 [1,25(OH)D] levels exceed the values of controls in some but not all hypercalciuric stone formers (HSF). We aimed to evaluate serum 1,25(OH)D levels, the expression of VDR, CYP27B1, and CYP24A1 hydroxylases in HSF in comparison with normocalciuric stone formers (NSF) and healthy subjects (HS). Blood samples, 24-h urine collections and a 3-day dietary record were obtained from 30 participants from each of the groups. The expression of VDR, CYP27B1, and CYP24A1 was measured by flow cytometry. HSF presented significantly higher urinary volume, sodium, magnesium, oxalate, uric acid, and phosphorus than NSF and HS. Calcium intake was lower in HSF versus NSF and HS (442 ± 41 vs 594 ± 42 and 559 ± 41 mg/day, respectively, p = 0.027). Ionized calcium was significantly lower in HSF than NSF (1.29 ± 0.0 vs 1.31 ± 0.0 mmol/L, p < 0.01). Serum 1,25(OH)D was significantly higher in HSF and NSF than HS (22.5 ± 1.2; 22.2 ± 1.2 vs 17.4 ± 1.2 pg/ml, p = 0.007) but serum 25(OH)D, PTH, klotho and plasma FGF-23 did not differ between groups. VDR expression was higher in HSF and NSF than HS (80.8 ± 3.2; 78.7 ± 3.3 vs 68.6 ± 3.2%, p = 0.023). Although CYP27B1 and CYP24A1 expressions were similar among all groups, the ratio of 1,25(OH)D/CYP24A1 was higher in HSF and NSF than in HS (1.43 ± 0.25 and 0.56 ± 0.10 vs 0.34 ± 0.06, p = 0.00). Stone formers, regardless of urinary calcium excretion, had higher VDR expression and 1,25(OH)D levels than HS, even in ranges considered normal. Higher 1,25(OH)D/CYP24A1 ratio suggested a lower degradation of 1,25(OH)D by CYP24A1 in HSF and NSF.

Keywords

Hypercalciuria Vitamin D receptor Nephrolithiasis CYP27B1 CYP24A1 

Notes

Acknowledgements

The authors thank Altay Alves Lino de Souza for his expert statistical assistance and advice. We also thank Maria Aparecida Dalboni, Caren Cristina Grabulosa and Silvia Regina Moreira for technical assistance. This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP—2016/25359-0), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES—Scholarship) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ—Grant 309045/2018-5, IPH).

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interest. The authors declare that the results presented in this paper have not been published previously in whole.

Ethical approval

All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study. Brazil Ethic Committee no 1.156.469 (Plataforma Brasil).

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Thalita Lima Melo
    • 1
  • Priscila Ligeiro Gonçalves Esper
    • 2
  • Lysien Ivania Zambrano
    • 3
    • 4
  • Milene Subtil Ormanji
    • 2
  • Fernanda Guedes Rodrigues
    • 1
  • Ita Pfeferman Heilberg
    • 2
    Email author
  1. 1.Nutrition Post Graduation ProgramUniversidade Federal de São PauloSão PauloBrazil
  2. 2.Nephrology DivisionUniversidade Federal de São PauloSão PauloBrazil
  3. 3.Department of Physiology, Cardiovascular Division, Escola Paulista de MedicinaUniversidade Federal de São PauloSão PauloBrazil
  4. 4.Department of Morphological SciencesUniversidad Nacional Autónoma de HondurasTegucigalpaHonduras

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