Kidney Week

Abstract: SA-PO270

Expression of Vitamin D Receptor, CYP27B1 and CYP24A1 Hydroxylases, and 1,25-Dihydroxyvitamin D3 Levels In Stone Formers

Session Information

• Bone and Mineral Metabolism: Calcium, Magnesium, Kidney Stones
  November 09, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 402 Bone and Mineral Metabolism: Clinical

Authors

• Melo, Thalita Lima, Universidade Federal de São Paulo, Sao Paulo, Brazil

Thalita Lima Melo,

• Esper, Priscila Ligeiro Gon?alves, Universidade Federal de São Paulo, Sao Paulo, Brazil

Priscila Ligeiro Gon?alves Esper,

• Zambrano, Lysien Ivania, Universidade Federal de São Paulo, Sao Paulo, Brazil

Lysien Ivania Zambrano,

• Ormanji, Milene Subtil, Universidade Federal de São Paulo, Sao Paulo, Brazil

Milene Subtil Ormanji,

• Rodrigues, Fernanda Guedes, Universidade Federal de São Paulo, Sao Paulo, Brazil

Fernanda Guedes Rodrigues,

• Heilberg, Ita Pfeferman, Universidade Federal de São Paulo, Sao Paulo, Brazil

Ita Pfeferman Heilberg,

Background

The underlying pathophysiological mechanisms for hypercalciuria such as increased intestinal calcium absorption, reduced renal tubular reabsorption and increased bone resorption are influenced by calciotropic hormones. The levels of 1,25(OH)₂D₃ exceed the values of controls in some but not all hypercalciuric stone formers and the expression of vitamin D receptor (VDR) remains controversial in human studies. We aimed to evaluate the serum 1,25(OH)₂D₃ levels and the expression of VDR and the regulatory enzymes CYP27B1 (1α-hydroxylase) and CYP24A1, responsible for vitamin D degradation, in hypercalciuric stone formers (HSF) and compare to normocalciuric stone formers (NSF) and healthy subjects (HS).

Methods

Blood samples, 24-hour urine collection and a 3-day dietary record were obtained from 30 participants of each of the groups. The expression of VDR, CYP27B1 and CYP24A1 in monocytes were measured by flow cytometry.

Results

HSF presented a significantly higher mean urinary volume, sodium, magnesium, oxalate, uric acid, and phosphorus than NSF and HS. Mean daily calcium intake was lower in HSF versus NSF and HS (442±41 vs 594±42 and 559±41 mg, 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)₂D₃ was significantly higher, even within normal ranges, in both HSF and NSF versus HS (22.5±1.2; 22.2±1.2 vs 17.4±1.2 pg/ml, p=0.007, respectively) but serum 25OHD₃, PTH, α-Klotho and plasma FGF-23 did not differ between groups. The VDR expression was higher in both HSF and NSF versus 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)₂D₃/CYP24A1 was higher in HSF and NSF than in HS (1.43±0.25 and 0.56±0.10 than 0.34±0.06, p=0.00).

Conclusion

Stone-formers, regardless of urinary calcium levels, had higher VDR expression and 1,25(OH)₂D₃ levels compared to HS. Higher 1,25(OH)₂D₃/CYP24A1 ratio suggested a lower degradation of 1,25(OH)₂D₃ by CYP24A1 in HSF and NSF.