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Clin Chim Acta. 2013 Sep 23;424:76-82. doi: 10.1016/j.cca.2013.05.016. Epub 2013 May 28.

Effects of sodium citrate on melamine-cyanuric acid mixture-induced urolithiasis in rats.

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  • 1Human Genetic Center, China Medical University Hospital, Taichung, Taiwan.



When melamine is used as an additive in infant formula, it may cause acute nephrotoxicity in humans as well as in other animals. This study was designed to examine the effects of a melamine-cyanuric acid mixture on cytotoxicity in vitro and rat-acute nephrotoxicity.


In the in vitro study, crystal formations created by the melamine-cyanuric acid mixture were evaluated in media with differing pH conditions over a 24-h period and co-treatment with sodium citrate to observe the crystal formation. In the animal study, rats were exposed to a melamine-cyanuric acid mixture (400 mg/kg, 1:1) via oral gavage 14 days and co-treated with sodium citrate to observe the crystal formation in rats.


Melamine-cyanuric acid mixture-induced crystal was pH dependent in a conditioned medium, and sodium citrate could decrease the crystal formation. Melamine-cyanuric acid-treated rats showed marked kidney swelling, vacuolization and necrosis in the proximal tubules, and numerous polarizable crystals were located in the distal segments, causing increases in kidney weight, serum BUN and creatinine. After co-treatment with sodium citrate, these increases can all be reversed. Moreover, the degrees of nephrotoxicity, proliferating of cell nuclear antigen protein and urolithiasis-related osteopontin were also decreased in the kidneys.


Sodium citrate could decrease melamine-cyanuric acid mixture-induced crystal formation that leads to urolithiasis and nephrotoxicity in rats. These results may provide a strategy for melamine-cyanuric acid-intoxication therapy in animal.

Copyright © 2013 Elsevier B.V. All rights reserved.


Melamine and cyanuric acid; Nephrotoxicity; Sodium citrate; Urolithiasis

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