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

摘要

Pathogenic accumulation of calcium (Ca) and phosphate (PO4) in vasculature is a sentinel of advancing cardiovascular disease in chronic kidney disease (CKD). This study sought to characterize acute distribution patterns of radiolabeled (PO4)-P-33 and Ca-45 in cardiovascular tissues of rats with CKD (0.25% dietary adenine). The disposition of (PO4)-P-33 and Ca-45 was assessed in blood and 36 tissues after a 10-minute intravenous infusion of one of the following: (i) PO4 pulse + tracer (PO4)-P-33; (ii) PO4 pulse + tracer Ca-45; or (iii) saline + tracer Ca-45 in CKD and non-CKD animals. After the infusion, (PO4)-P-33 in blood was elevated (2.3x at 10 minutes, 3.5x at 30 minutes, p 0.05) in CKD compared with non-CKD. In contrast, there was no difference in clearance of Ca-45 from the blood. Compared with controls, CKD rats had a markedly increased (PO4)-P-33 incorporation in several tissues (skeletal muscle, 7.8x; heart, 5.5x), but accrual was most pronounced in the vasculature (24.8x). There was a significant, but smaller, increase in Ca-45 accrual in the vasculature of CKD rats (1.25x), particularly in the calcified rat, in response to the acute phosphate load. Based on the pattern of tissue uptake of (PO4)-P-33 and Ca-45, this study revealed that an increase in circulating PO4 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 PO4 pulse provides evidence of significant tissue-specific susceptibility to calcification. (c) 2018 American Society for Bone and Mineral Research.