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Vitamin D metabolism and current options for therapeutic activation of vitamin D receptor in patients with chronic kidney disease or renal failure


Authors: S. Dusilová Sulková 1,2
Authors‘ workplace: Hemodialyzační středisko FN, Hradec Králové, vedoucí lékařka prof. MUDr. Sylvie Dusilová Sulková, DrSc., MBA 1;  Klinika nefrologie, Transplantcentrum Institutu klinické a experimentální medicíny Praha, přednosta prof. MUDr. Ondřej Viklický, CSc. 2
Published in: Vnitř Lék 2012; 58(11): 839-849
Category: Reviews

Overview

Chronic kidney disease (CKD), and chronic renal failure in particular, is associated with vitamin D deficiency and with a disorder of all metabolic processes that are associated with vitamin D. Calcidiol levels are often low. At present, efforts are made to test and to pharmacologically modulate its levels and thus to contribute to greater availability of the substrate for external calcitriol production. Calcitriol production is reduced in CKD patients not only as a consequence of diminishing functional renal parenchyma but also as a consequence of 1-α-hydroxylase inhibition by FGF-23 and other factors. On the other hand, although parathormone (PTH) increases renal production of calcitriol, it also causes secondary hyperparathyroidism. Synthetic calcitriol (or α-calcidiol) supresses PTH production and is used to treat secondary hyperparathyroidism. This approach is often associated with adverse increase in calcaemia and phosphataemia as the effect on parathyroid glands is associated with an effect on the gastrointestinal tract where calcium and phosphor absorption is increased by calcitriol. Synthetic analogues of vitamin D inhibit parathyroid gland but have significantly lower effect on gastrointestinal tract. Paricalcitol is a selective VDR (vitamin D receptor) activator, used for targeted suppression of parathyroid glands. Vitamin D deficiency in general population is associated, at least in epidemiological studies, with a range of medical complications and the same also applies to patients with renal disease. Although randomised studies are not available, clinical observational studies repeatedly showed treatment with VDR activators to be associated with better prognosis. As other fields of medicine, nephrology currently pays a great attention to vitamin D and vitamin D receptor activation.

Klíčová slova:
calcitriol – calcidiol – paricalcitol – chronic kidney disease – chronic renal failure – vitamin D receptor – secondary hyperparathyroidism


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