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CYP24A1 gene, kidney disease, and vitamin D - May 2011

CYP24A1 and kidney disease

Curr Opin Nephrol Hypertens. 2011 May 22.
Petkovich M, Jones G.
aDivision of Cancer Biology and Genetics, Cancer Research Institute, Queen's University, Kingston, Canada bDepartment of Research and Development, Cytochroma Inc., Markham, Canada cDepartments of Biochemistry and Medicine, Queen's University, Kingston, Ontario, Canada.

PURPOSE OF REVIEW:
Patients with chronic renal disease have elevated serum phosphate levels, elevated fibroblast-like growth factor 23 (FGF-23), and declining vitamin D status. These changes are related and may be responsible for elevated 25-hydroxyvitamin D-24-hydroxylase (CYP24A1) and dysfunctional vitamin D metabolism. This review focuses on the biochemistry and pathophysiology of CYP24A1 and the utility of blocking this enzyme with CYP24A1 inhibitors in chronic kidney disease (CKD) patients.

RECENT FINDINGS:
CYP24A1 is the cytochrome P450 enzyme that catalyzes the conversion of 25-hydroxyvitamin D3 (25-OHD3) and its hormonal form, 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], into 24-hydroxylated products targeted for excretion. The CYP24A1-null phenotype is consistent with the catabolic role of CYP24A1. A number of polymorphisms of CYP24A1 have recently been identified. New data from the uremic rat and humans suggest that dysfunctional vitamin D metabolism is due to changes in CYP24A1 expression caused by phosphate and FGF-23 elevations.

SUMMARY:
Changes in serum phosphate and FGF-23 levels in the CKD patient increase CYP24A1 expression resulting in decreased vitamin D status. Vitamin D deficiency may exacerbate defective calcium and phosphate homeostasis causing renal osteodystrophy and contribute to the other complications of renal disease. These findings argue for increased focus on correcting vitamin D deficiency in CKD patients by blocking CYP24A1 activity.

PMID: 21610497 full text online
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See also VitaminDWiki

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