The Vitamin D Metabolite Diagnostic Ratio Associates With Phenotypic Traits of Idiopathic Hypercalciuria.

Abstract

Introduction:

Underlying mechanisms for hypercalciuria remain unknown in most cases; thus, the designation "idiopathic." 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) vitamin D3/total 24,25 (OH)2 vitamin D ratio; VMDR), and the phenotype of participants in 2 observational cohorts of kidney stone formers, the Swiss Kidney Stone Cohort (SKSC) and the Bern Kidney Stone Registry (BKSR). Circulating 25(OH)- and 24,25 (OH)2 vitamin D were quantified using a validated liquid chromatography tandem mass spectrometry assay.

Results:

A total of 974 participants were included in the analysis. We found a positive association of VMDR (and hence negative association of CYP24A1 activity) with total (β 0.009 mmol/l; 95% confidence interval [CI]: 0.002, 0.016; P = 0.02) and ionized plasma calcium (β 0.005 mmol/l; 95% CI: 0.002, 0.008; P < 0.01), absolute and fractional excretion of urinary calcium (β 0.054 mmol/24h; 95% CI: 0.010, 0.097; P = 0.02 and β 0.046%; 95% CI: 0.018, 0.074; P < 0.01, respectively). Further, VMDR was associated with an increased likelihood of forming calcium oxalate dihydrate stones (Odds ratio [OR] 1.64; 95% CI: 1.22, 2.35; P < 0.01) and reduced bone mineral density (BMD) at the femoral neck (β -0.005 g/cm2; 95% CI: -0.010, -0.001; P = 0.04). The described associations became stronger when the analysis was confined to idiopathic calcium stone formers.

Conclusion:

Our study reveals that CYP24A1 activity, estimated by VMDR, is associated with clinical traits previously linked to idiopathic hypercalciuria.

• Authors: Nasser A Dhayat, Cédric Mattmann, Harald Seeger, Alexander Ritter, Thomas Ernandez, Catherine Stoermann-Chopard, Florian Buchkremer, Stephan Segerer, Beat Roth, Gregoire Wuerzner, Carsten A Wagner, Olivier Bonny, Albrecht W Popp, Bruno Vogt, Matteo Bargagli, Daniel G Fuster
• Journal: Kidney international reports (Kidney Int Rep) Vol. 9 Issue 4 Pg. 1072-1082 (Apr 2024) ISSN: 2468-0249 [Electronic] United States
• PMID: 38765596 (Publication Type: Journal Article)
• Copyright: © 2024 International Society of Nephrology. Published by Elsevier Inc.