Jun 16 2010
- Dysregulation of CYP24 linked to chronic kidney disease -
Cytochroma today announced the publication of new data from studies in a preclinical model indicating that chronic kidney disease (CKD) is associated with markedly increased expression of the vitamin D catabolic enzyme, CYP24, which contributes to vitamin D insufficiency and resistance to vitamin D therapy. Parallel analysis of kidney biopsies obtained from CKD patients confirmed abnormal CYP24 expression in human disease as well. The findings were published in Kidney International's advance online publication, and will appear in a forthcoming print edition of Kidney International.
"Our research raises the possibility that aberrantly elevated CYP24 accelerates progression of kidney disease," stated Dr. Martin Petkovich, Cytochroma's Chief Scientific Officer. "Adequate vitamin D hormone supply will normally suppress kidney inflammation and reduce the associated risk of irreversible fibrosis. CYP24, however, inactivates vitamin D hormone and deprives the kidneys of adequate supply. CYP24 also inactivates all currently available vitamin D therapies, making it difficult to treat the hormone deficit in the kidneys."
This newly published research examined CYP24 regulation in relation to vitamin D status in normal rats and in adenine-treated uremic rats, a preclinical model of CKD. As expected, when normal rats were fed a vitamin D deficient diet, CYP24 expression decreased in order to preserve existing vitamin D stores. In contrast, CYP24 expression increased in rats with renal impairment and remained elevated when these rats were fed a vitamin D deficient diet, demonstrating that kidney damage significantly altered the regulation of CYP24 expression. Increased CYP24 expression was separately confirmed in kidney biopsies obtained from CKD patients, suggesting that CYP24 is similarly dysregulated in human renal disease.
These findings indicate that new vitamin D products which resist catabolism by CYP24 and/or minimize CYP24 expression may offer significant advantages over currently available therapies for CKD patients.
Source: CYTOCHROMA