Kidney Week

Abstract: SA-PO301

CYP24A1 Activity Associates with Phenotypic Traits in Idiopathic Hypercalciuria

Session Information

• Bone and Mineral Metabolism: Stones, Calcifications, Case Reports
  November 04, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Bone and Mineral Metabolism

• 502 Bone and Mineral Metabolism: Clinical

Authors

• Fuster, Daniel G., Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

Daniel G. Fuster,

• Bargagli, Matteo, Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland

Matteo Bargagli,

• Bonny, Olivier, Service of Nephrology, Lausanne University Hospital, Lausanne, Switzerland

Olivier Bonny,

Background

Hypercalciuria is the most frequent abnormality in kidney stone formers. The underlying mechanisms remain unknown in most cases, hence the designation “idiopathic hypercalciuria”. We hypothesized that the Vitamin D-inactivating enzyme CYP24A1 contributes to the pathogenesis of hypercalciuria in kidney stone formers.

Methods

We conducted association analyses between CYP24A1 activity, estimated by the Vitamin D metabolite diagnostic ratio (25(OH)-/24,25 (OH)₂ Vitamin D₃ ratio; VMDR), and the phenotype of participants in two observational cohorts of kidney stone formers, the Swiss Kidney Stone Cohort and the Bern Kidney Stone Registry. Linear and logistic regression models adjusted for multiple confounders, including plasma 25(OH) Vitamin D₃, were applied. Plasma 25(OH)- and 24,25 (OH)₂ Vitamin D₃ were quantified using an established, highly sensitive and specific LC-MS/MS assay.

Results

In total, 974 participants were included in the analysis. After multivariable adjustment, a higher VMDR (i.e. lower CYP24A1 activity) was associated with higher total plasma calcium (β 0.07; 95% CI 0.01, 0.14; p = 0.02), ionized calcium (β 0.11; 95% CI 0.03, 0.18; p < 0.01) and absolute and fractional excretion of urinary calcium (β 0.06; 95% CI 0.00, 0.11; p = 0.04 and β 0.10; 95% CI 0.04, 0.16; p < 0.01, respectively). A higher VMDR was further associated with an increased risk of forming stones composed of calcium oxalate dihydrate (Odds ratio 1.64; 95% CI 1.22, 2.35; p < 0.01) and a reduced bone mineral density at the femoral neck (β -0.07; 95% CI 0.14, -0.01; p = 0.04). VMDR was not associated with plasma or urinary phosphate, 1,25 (OH)₂ Vitamin D₃ or parathyroid hormone.

Conclusion

Our study reveals that CYP24A1 activity is associated with traits previously linked to idiopathic hypercalciuria.