Ergocalciferol Therapy in Calcidiol Deficient, Hemodialysis Patients on Therapeutic Doses of Paricalcitol

Overview

The objective of this study is to determine the effects of cholecalciferol treatment on inflammation and insulin resistance, in patients on hemodialysis that are previously treated with paricalcitol. Cholecalciferol is produced by the action of sunlight on a cholesterol precursor in the skin. This compound is then converted to calcidiol (25(OH) D3) in the liver, whereupon calcidiol is converted in the kidney to calcitriol (1,25(OH)2D3), the active form of vitamin D. However, recently it has been shown that deficiency of either calcidiol or calcitriol is associated with inflammation, insulin resistance and increased mortality in the general population. Furthermore, when both calcidiol and calcitriol were deficient, the mortality risk was much higher than the deficiency of either alone. A possible explanation is that some of the non-renal tissues might critically depend on the endogenous conversion of calcidiol to calcitriol and not on circulating levels of calcitriol. Thus, low circulating levels of calcidiol might be associated with tissue level functional calcitriol deficiency despite adequate circulating levels of calcitriol. Therefore, the hypothesis is that: 1. In non-diabetic hemodialysis (HD) patients treated with therapeutic doses of paricalcitol (an analog of calcitriol), calcidiol deficiency is associated with inflammation and insulin resistance and 2. In calcidiol deficient, non-diabetic HD patients with inflammation and treated with therapeutic doses of paricalcitol, cholecalciferol will reverse the calcidiol deficiency and thereby, reduce inflammation and insulin resistance. Interleulin-6 (IL-6) is thought to play a central role in insulin resistance by down-regulating glucose transporter-4 messenger RNA. Furthermore, IL-6 levels are significantly negatively associated with calcidiol levels, therefore will be measured as the primary outcome.