Calcium and Phosphate Disposition in Chronic Kidney Disease
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Date
2015-09-08
Authors
Zelt, Jason
Keyword
Phosphate , Vascular Calcification , Chronic Kidney Disease , Calcium
Abstract
Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). Vascular calcification (VC) is the most prevalent form of cardiovascular disease in this population and the attributable cardiovascular mortality is 10-100 times greater than healthy individuals. Mineral imbalance is a hallmark of progressing CKD, which greatly increases the propensity for VC. Specifically, pathogenic VC has been consistently linked to altered phosphate metabolism in CKD patients. Despite the critical role of phosphate in cell biology, there are significant gaps in knowledge regarding the in vivo kinetics of circulating phosphate.
A modified adenine model of CKD was used to characterize the disposition of circulating phosphate and calcium from the circulation to tissues. Studies used radiolabeled phosphate and calcium infusions to demonstrate that acute, non-renal phosphate handling is impaired in CKD and is manifested as an amplified phosphate pulse following administration. This pulse, rather than hyperphosphatemia per se, generated an increased transfer of phosphate and calcium selectively into vascular tissues. The maladaptive nature of this mineral handling process reveals an important early mechanism in both the initiation and progression of vascular calcification in CKD.
This mechanism will potentially generate new therapeutic targets for reducing the impact of phosphate on vascular calcification outcomes in CKD. Although the management of circulating phosphate levels in CKD patients is clinically recognized to attenuate soft tissue calcification, the present findings indicate for the first time that targeting the oscillations in phosphate, rather than the circulating phosphate level per se, is likely to be more relevant approach for reducing the morbidity linked to the progression of vascular calcification.