Acute Tissue Mineral Deposition in Response to a Phosphate Pulse in Experimental CKD.

Pathogenic accumulation of calcium (Ca) and phosphate (PO ) in vasculature is a sentinel of advancing cardiovascular disease in chronic kidney disease (CKD). This study sought to characterize acute distribution patterns of radiolabeled PO and Ca in cardiovascular tissues of rats with CKD (0.25% dietary adenine). The disposition of PO and Ca was assessed in blood and 36 tissues after a 10-minute intravenous infusion of one of the following: (i) PO  pulse + tracer PO ; (ii) PO  pulse + tracer Ca; or (iii) saline + tracer Ca in CKD and non-CKD animals. After the infusion, PO in blood was elevated (2.3× at 10 minutes, 3.5× at 30 minutes, p < 0.05) in CKD compared with non-CKD. In contrast, there was no difference in clearance of Ca from the blood. Compared with controls, CKD rats had a markedly increased PO incorporation in several tissues (skeletal muscle, 7.8×; heart, 5.5×), but accrual was most pronounced in the vasculature (24.8×). There was a significant, but smaller, increase in Ca accrual in the vasculature of CKD rats (1.25×), particularly in the calcified rat, in response to the acute phosphate load. Based on the pattern of tissue uptake of PO and Ca, this study revealed that an increase in circulating PO is an important stimulus for the accumulation of these minerals in vascular tissue in CKD. This response is further enhanced when vascular calcification is also present. The finding of enhanced vascular mineral deposition in response to an acute PO  pulse provides evidence of significant tissue-specific susceptibility to calcification. © 2018 American Society for Bone and Mineral Research.