Early Events Involving Glomerular Calcification Induced by Dibasic Sodium Phosphate Solution in Rats

• Published in: Journal of Toxicologic Pathology Vol. 21; no. 4; pp. 229 - 237
• Main Authors: Tsuchiya, Noriko, Torii, Mikinori, Narama, Isao, Matsui, Takane
• Format: Journal Article
• Language: English
• Published: Tokyo JAPANESE SOCIETY OF TOXICOLOGIC PATHOLOGY 01-01-2008; The Japanese Society of Toxicologic Pathology; Japan Science and Technology Agency
• Subjects: calcification; electron microscopy; glomerulus; immunohistochemistry; Na2HPO4; rat
• ISSN: 0914-9198; 1881-915X; 1347-7404
• DOI: 10.1293/tox.21.229

To investigate the early changes involved in glomerular calcification, 360 mM Na2HPO4 was administered to rats at 8 mL/kg once daily via the tail vein singly or repeatedly. Urinalysis was carried out on days 1, 3, 5 and 8 of dosing, and rats were sacrificed on days 2, 4 and 9 for histopathological and electron microscopic examination of the kidneys. Following single dosing, there were no gross or histological findings, but electron microscopy revealed a number of vacuoles scattered within the Bowman's space. On day 4, minimal and focal mineralization was observed within the parietal epithelial cells. On day 9, mineralization was minimal to mild and localized within the parietal epithelial cells and glomerular basement membrane. Hypertrophy and increased mitotic figures were also frequently observed in the parietal epithelial cells. Low-density lamellar structures with effacement of podocytes, an increased number of microvilli and large amounts of debris filling the Bowman's space were the main electron microscopic changes on days 4 and 9. Increased urinary protein excretion correlated well with the glomerular changes. Immunohistochemically, increased expression of desmin and decreased expression of podoplanin were evident in glomeruli on day 9. The numbers of PCNA-positive podocytes and parietal epithelial cells showed a tendency to increase on day 9. These results suggest that the onset of glomerular calcification is preceded by primary podocyte damage.