Is vitamin D3 bad for the kidney?

Abstract

Active vitamin D3 {1,25-dihydroxyvitamin D3 [1,25(OH)2D3], calcitriol} is a hormone best known for its role in modulating mineral balance. Its synthesis involves several steps, including a hepatic hydroxylation to calcidiol {25-hydroxyvitamin D [25(OH)D3]}, requiring the cytochrome P450 enzyme CYP2R1, and final activation in the kidney by CYP27B1, mostly expressed in proximal tubules. Also, the degradation of calcitriol and calcidiol is performed by CYP24A1 in the proximal tubule [1]. Importantly, only 1,25(OH)2D3 exerts significant biological activity, all other forms of vitamin D3 (i.e. intermediate metabolites of synthesis and degradation) are thought to have minimal or no biologic activity [1, 2]. As expected for a hormone that has many functions in controlling mineral homeostasis, the synthesis and degradation of calcitriol is tightly regulated by many calci- and phosphatotropic factors, including parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), calcium and phosphate. In addition, immune cytokines modulate calcitriol levels...