The metabolism of 1,25(OH)2D3 in clinical and experimental kidney disease

Chronic kidney disease (CKD) results in calcitriol deficiency and altered vitamin D metabolism. The objective of this study was to assess the 24-hydroxylation-mediated metabolism of 25(OH)D-3 and 1,25(OH)(2)D-3 in a cross-sectional analysis of participants with a range of kidney function assessed by precise measured GFR (mGFR) (N = 143) and in rats with the induction and progression of experimental kidney disease. Vitamin D metabolites were assessed with LC-MS/MS. Circulating measures of 24-hydroxylation of 25(OH)D-3 (24,25(OH)(2)D-3:25(OH)D-3) precisely decreased according to mGFR in humans and progressively in rats with developing CKD. In contrast, the 1,24,25(OH)3D3: 1,25(OH)(2)D-3 vitamin D metabolite ratio increased in humans as the mGFR decreased and in rats with the induction and progression of CKD. Human participants taking cholecalciferol had higher circulating 1,24,25(OH)(3)D-3, despite no increase of 1,25(OH)(2)D-3. This first report of circulating 1,24,25(OH)(3)D-3 in the setting of CKD provides novel insight into the uniquely altered vitamin D metabolism in this setting. A better understanding of the uniquely dysfunctional catabolic vitamin D profile in CKD may guide more effective treatment strategies. The potential that 24-hydroxylated products have biological activity of is an important area of future research.

Automated summary

Chronic kidney disease (CKD) leads to altered vitamin D metabolism, with decreasing levels of 24-hydroxylated products. The unique vitamin D metabolism in CKD may guide more effective treatment strategies.