1D.08

Abstract

Objective: Cardiovascular disease is a major cause of mortality in patients with chronic kidney disease (CKD). Elevated serum phosphate and FGF23 are associated with cardiovascular disease in patients with CKD. Current therapy focuses on decreasing serum phosphorus using phosphate binders. PA21 is a new iron-based phosphate binder. Few studies have analysed how to suppress FGF23 up-regulation using phosphate binders. To evaluate the effects of PA21 compared with other phosphate binders as lanthanum carbonate (La) and sevelamer carbonate (Se) on serum FGF23, phosphorus, calcium, iPTH concentrations and to investigate a potential effect on the development of vascular calcifications in an adenine-induced rat model of CRF. Design and method: After induction of chronic renal failure through a 4 week adenine-diet, renal function was significantly impaired in all groups. All uremic rats developed severe hyperphosphatemia and serum PTH increased significantly. Phosphate binders were then given for 4 weeks to all uremic rats, except for the uremic control rats. The concentration of each binder (% of binder added to the diet) was chosen to deliver approximately the same amount of active pharmaceutical moiety to each rat: PA21 5% (corresponding to 1% iron), La 2% (1% lanthanum), Se 1.5% (1% sevelamer). A computer-assisted automated quantitative measurement was used to assess the degree of calcification from von Kossa stained vessel sections. Results: Hyperphosphatemia and increased serum PTH levels were controlled in the phosphate binder treated groups to the same extent. PA21 was the only phosphate binder that was associated with a decrease of FGF23. In uremic control rats, vascular calcifications were more prominently present in the thoracic aorta compared to the carotids and the abdominal aorta. Vascular calcifications of thoracic aorta were significantly decreased by the three phosphate binders to a similar extent. PA21 was more efficient than lanthanum carbonate to prevent calcifications in the upper part of the thoracic aorta. Conclusions: PA21 was as effective in the control of hyperphosphatemia, secondary hyperparathyroidism and vascular calcifications as La and Se. The role of FGF23 as a potential factor of calcification needs to be confirmed.