Expression of vitamin D receptor, CYP27B1 and CYP24A1 hydroxylases and 1,25-dihydroxyvitamin D-3 levels in stone formers

Author(s)

Melo, Thalita Lima ; Goncalves Esper, Priscila Ligeiro ; Zambrano, Lysien Ivania ; Ormanji, Milene Subtil ; Rodrigues, Fernanda Guedes ; Heilberg, Ita Pfeferman

• Document type: Journal article
• Source: UROLITHIASIS; v. 48, n. 1, p. 8-pg., 2019-11-06.

Abstract

The expression of vitamin D receptor (VDR) and 1,25-dihydroxyvitamin D-3 [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. (AU)

• FAPESP's process: 16/25359-0 - Evaluation of bone microarchitecture and finite element and their association with anthropometric, densitometric biochemical and hormonal parameters in hypercalciuric nephrolithiasis patients
• Grantee: Ita Pfeferman Heilberg
• Support Opportunities: Regular Research Grants