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Acute Tissue Mineral Deposition in Response to a Phosphate Pulse in Experimental CKD
Author(s) -
Zelt Jason GE,
Svajger Bruno A,
Quinn Kieran,
Turner Mandy E,
Laverty Kimberly J,
Shum Bonnie,
Holden Rachel M,
Adams Michael A
Publication year - 2019
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.3572
Subject(s) - phosphate , medicine , calcium , kidney disease , calcification , kidney , endocrinology , saline , vascular tissue , chemistry , biology , biochemistry , botany
Pathogenic accumulation of calcium (Ca) and phosphate (PO 4 ) in vasculature is a sentinel of advancing cardiovascular disease in chronic kidney disease (CKD). This study sought to characterize acute distribution patterns of radiolabeled 33 PO 4 and 45 Ca in cardiovascular tissues of rats with CKD (0.25% dietary adenine). The disposition of 33 PO 4 and 45 Ca was assessed in blood and 36 tissues after a 10‐minute intravenous infusion of one of the following: (i) PO 4 pulse + tracer 33 PO 4 ; (ii) PO 4 pulse + tracer 45 Ca; or (iii) saline + tracer 45 Ca in CKD and non‐CKD animals. After the infusion, 33 PO 4 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 45 Ca from the blood. Compared with controls, CKD rats had a markedly increased 33 PO 4 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 45 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 33 PO 4 and 45 Ca, this study revealed that an increase in circulating PO 4 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 4 pulse provides evidence of significant tissue‐specific susceptibility to calcification. © 2018 American Society for Bone and Mineral Research.