Vitamin D deficiency

Chronic kidney disease: vitamin D deficiency

Cholecalciferol (vitamin D3) is either acquired as food constituent or synthesized in the skin under influence of ultraviolet illumination. Cholecalciferol is modified to more active forms by the addition of two hydroxyl groups. The first hydroxylation occurs unregulated in the liver and yields calcidiol (25(OH)D3). Calcidiol is further hydroylated in the kidney catalysed by 1α-hydroxylase, an enzyme localized in proximal tubule cells. The activity of this enzyme is stimulated by PTH. See the graphic below.

Patients with CKD may have calcidiol deficiency by factors as ageing, lack of sunlight exposure, diabetes and proteinuria. This shortage of substrate leads, together with loss of renal mass and functional suppression of 1α-hydroxylase by hyperphosphatemia to calcitriol deficiency.

Both calcidiol and calcitriol deficiency accounts for diminished activation of the intracellular located vitamin D receptor (VDR). This results in a decrease of the intestinal calcium absorption and also directly an increase in PTH secretion. Insufficient activation of the VDR may also lead to low bone formation rates, vascular calcification, left ventricular hypertrophy, insulin resistance, hypertension and predisposition to inflammation and infection.

Treatment of vitamin D deficiency includes maintaining adequate calcidiol levels by cholecalciferol. Calcitriol deficiency in severe CKD should be treated by the prohormone alfacalcidol, which needs hydroxylation in the liver or the VDR activator paricalcitol.


What kind of receptor is the vitamin D receptor (VDR)?