A randomised clinical study of alfacalcidol and paricalcitol.

Abstract

Vitamin D analogs are used for treatment of secondary hyperparathyroidism in patients with chronic kidney disease in order to prevent renal osteodystrophy, bone fracture and pain. Calcium and phosphate levels increase with increasing doses of vitamin D analogs and are associated with increased risk of vascular calcification and cardiovascular morbidity and mortality. Therefore, in everyday clinical practice, hypercalcemia and hyperphosphatemia often limits the ability to suppress secondary hyperparathyroidism in patients with chronic kidney disease. In Denmark, alfacalcidol and paricalcitol are the most frequently used vitamin D analogs. The present thesis describes the first comparative study of alfacalcidol and paricalcitol and their ability to control the disturbances in the mineral metabolism in hemodialysis patients. In a multicenter randomised 2 × 16-week cross-over study (n = 86), with a 6-week wash out period preceding and between treatment periods, intravenous alfacalcidol and paricalcitol were given by forced titration (50% dose increase) every second week, until parathyroid hormone were sufficiently suppressed or ionised calcium and/or phosphate levels were elevated. Due to the presence of a period effect, only data from the initial 16-week intervention period (n = 80) were available for statistical tests of effect on parathyroid hormone. The proportion of patients achieving a 30% decrease in parathyroid hormone over the last four weeks was similar in the two groups (alfacalcidol 82%, paricalcitol 93% (p = 0.180)). A significant interaction effect between baseline parathyroid hormone and treatment was found (p = 0.012), suggesting the effects of alfacalcidol to be independent of baseline parathyroid hormone level, whereas paricalcitol to be more efficient at low than at high baseline levels. There were no differences in incidence of hypercalcemia and hyperphosphatemia. FGF23 increases renal phosphate excretion and decreases levels of 1,25-dihydroxyvitamin D. FGF23 is elevated in hemodialysis patients by mechanisms not fully understood. We explored the influence of alfacalcidol and paricalcitol on FGF23 in stored blood samples from the beginning and the end of each treatment period. FGF23 increased significantly and equally during treatment with alfacalcidol and paricalcitol. Furthermore, we found baseline FGF23 to predict PTH levels after 16 weeks of vitamin D analog treatment. Overall, alfacalcidol and paricalcitol are equal candidates for treatment of disturbances in mineral metabolism in hemodialysis patients.