PTH suppression by calcitriol does not predict off ‐target actions in experimental CKD

AbstractVitamin D receptor agonist (VDRA) therapy for PTH suppression is a mainstay for patients with severe CKD. Calcitriol (1,25 ‐(OH)2D3) is a former first ‐line VDRA in CKD treatment. However, a consequence of its use in CKD is accelerated vascular calcification (VC). An experimental CKD model was used to determine whether altering the calcitriol delivery profile to obtain different PTH suppression levels could improve vascular health outcomes. High adenine diet (0.25%) was used to generate experimental CKD in rats. CKD rats were treated using different calcitriol dosing strategies: (a) 20 ng/kg SD (n = 8), (b) 80 ng/kg SD (n = 8), (c) 5 ng/kg QID (n = 9), or (d) 20 ng/kg QID (n = 9). Multiple targets of calcitriol were assessed wh ich include arterial calcium and phosphate as well as circulating calcium, phosphate, PTH, FGF‐23, VWF, and vitamin D metabolome. PTH suppression occurred dose‐dependently after 1‐week calcitriol treatment (P <  .01), but the suppressive effect was lost over time. Both VC and circulating FGF‐23 increased >  10× in all calcitriol‐treated rats (P <  .05 andP <  .001, respectively); similarly, circulating VWF increased at all time points (P <  .05). Ad‐hoc analysis of CKD morbidities in treated rats indicated no differences in negative outcomes based on PTH suppression level (minimal‐, target‐, and over‐). Comparing different calcitriol dosing strategies revealed the following: (a) despit...
Source: Pharmacology Research and Perspectives - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL ARTICLE Source Type: research