Figure 1.

Altered vitamin D metabolism in the course of kidney disease progression. In chronic kidney disease progression, decreased renal mass limits the amount of 1α-hydroxylase in renal proximal tubular cells. In addition, decreases in glomerular filtration rate (GFR) and low megalin content contribute to impaired 25(OH)D uptake and protein reabsorption. Moreover, increased levels of serum level of phosphate (P), fibroblast growth factor 23 (FGF23), N-terminally truncated parathyroid hormone (PTH) fragments, and uremic toxins, along with kidney function decline may contribute to the suppressed activation of 1α-hydroxylase, resulting in decreased levels of 1,25(OH)₂D. Also, increased FGF23 upregulates the expression of 24-hydroxylase, resulting in the catabolism of 1,25(OH)₂D to the inactive form of vitamin D, 1,24,25(OH)₃D. DBP, vitamin D binding protein; VDR, vitamin D receptor, IDBP3, intracellular vitamin D binding protein 3.