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

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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.

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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).

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Authors and Affiliations

  1. Nutrition Post Graduation Program, Universidade Federal de São Paulo, São Paulo, Brazil

    Thalita Lima Melo & Fernanda Guedes Rodrigues

  2. Nephrology Division, Universidade Federal de São Paulo, Rua Botucatu 740, São Paulo, SP, 04023-900, Brazil

    Priscila Ligeiro Gonçalves Esper, Milene Subtil Ormanji & Ita Pfeferman Heilberg

  3. Department of Physiology, Cardiovascular Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, São Paulo, Brazil

    Lysien Ivania Zambrano

  4. Department of Morphological Sciences, Universidad Nacional Autónoma de Honduras, Tegucigalpa, Honduras

    Lysien Ivania Zambrano

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  1. Thalita Lima Melo
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Melo, T.L., Esper, P.L.G., Zambrano, L.I. et al. Expression of vitamin D receptor, CYP27B1 and CYP24A1 hydroxylases and 1,25-dihydroxyvitamin D3 levels in stone formers. Urolithiasis 48, 19–26 (2020). https://doi.org/10.1007/s00240-019-01163-9

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