The serum 24,25-dihydroxyvitamin D concentration, a marker of vitamin D catabolism, is reduced in chronic kidney disease.

Abstract

Chronic kidney disease is characterized, in part, as a state of decreased production of 1,25-dihydroxyvitamin D (1,25(OH)(2)D); however, this paradigm overlooks the role of vitamin D catabolism. We developed a mass spectrometric assay to quantify serum concentration of 24,25-dihydroxyvitamin D (24,25(OH)(2)D), the first metabolic product of 25-hydroxyvitamin D (25(OH)D) by CYP24A1, and determined its clinical correlates and associated outcomes among 278 participants with chronic kidney disease in the Seattle Kidney Study. For eGFRs of 60 or more, 45-59, 30-44, 15-29, and under 15 ml/min per 1.73 m(2), the mean serum 24,25(OH)(2)D concentrations significantly trended lower from 3.6, 3.2, 2.6, 2.6, to 1.7 ng/ml, respectively. Non-Hispanic black race, diabetes, albuminuria, and lower serum bicarbonate were also independently and significantly associated with lower 24,25(OH)(2)D concentrations. The 24,25(OH)(2)D concentration was more strongly correlated with that of parathyroid hormone than was 25(OH)D or 1,25(OH)(2)D. A 24,25(OH)(2)D concentration below the median was associated with increased risk of mortality in unadjusted analysis, but this was attenuated with adjustment for potential confounding variables. Thus, chronic kidney disease is a state of stagnant vitamin D metabolism characterized by decreases in both 1,25(OH)(2)D production and vitamin D catabolism.

• Authors: Cortney R Bosworth, Gregory Levin, Cassianne Robinson-Cohen, Andrew N Hoofnagle, John Ruzinski, Bessie Young, Stephen M Schwartz, Jonathan Himmelfarb, Bryan Kestenbaum, Ian H de Boer
• Journal: Kidney international (Kidney Int) Vol. 82 Issue 6 Pg. 693-700 (Sep 2012) ISSN: 1523-1755 [Electronic] United States
• PMID: 22648296 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• PTH protein, human
• Parathyroid Hormone
• Vitamin D
• 25-hydroxyvitamin D
• Steroid Hydroxylases
• CYP24A1 protein, human
• Vitamin D3 24-Hydroxylase

Topics

• Black or African American
• Aged
• Biomarkers (blood)
• Comorbidity
• Cross-Sectional Studies
• Down-Regulation
• Female
• Glomerular Filtration Rate
• Humans
• Hyperparathyroidism, Secondary (blood, ethnology, mortality)
• Kaplan-Meier Estimate
• Kidney (physiopathology)
• Linear Models
• Male
• Mass Spectrometry
• Middle Aged
• Multivariate Analysis
• Parathyroid Hormone (blood)
• Prognosis
• Proportional Hazards Models
• Renal Insufficiency, Chronic (blood, ethnology, mortality, physiopathology)
• Risk Assessment
• Risk Factors
• Steroid Hydroxylases (metabolism)
• Vitamin D (analogs & derivatives, blood)
• Vitamin D3 24-Hydroxylase
• Washington (epidemiology)