The objective of this study is to understand pathogenesis of
melamine-related
kidney stone formation. We investigated the characterization of renal tubular cell under exposure to a mixture of
melamine and
cyanuric acid in vivo. Male Sprague-Dawley rats were separated into two experimental groups. Treatment group was administered daily with a standard commercial diet mixing with
melamine and
cyanuric acid, and control group was given a normal diet. Rat kidney specimens were stained with
hematoxylin/
eosin and the crystals were examined using a polarizing microscope. Renal tubular epithelial cells were observed by transmission electron microscopy. Semiquantitative RT-PCR assay was performed to determine
monocyte chemoattractant protein-1 (MCP-1)
mRNA expression, a
protein in response to various proinflammatory stimuli. Apoptotic cells were examined by TUNEL assay.
Melamine-associated crystals formed in glomerulus and wide renal tubule segment including proximal convoluted renal tubules, distal convoluted renal tubules, the limb loops of Henle and medullary collecting ducts in the cortex and medulla. Light microscopy results showed that the crystals lead to tubular lumen dilatation and tubular epithelial cell
necrosis. It was observed that nucleus of renal tubular epithelial cells became irregular outlines and condensed, lysosomal-related structures increased, and integrity of renal tubule was deficient under electron microscopy. Apoptotic cells were noted widely in cortex and medulla. MCP-1
mRNA expression was significantly increased in the
melamine and
cyanuric acid-administrated group. Renal tubular epithelial cell injury, apoptosis and
inflammation are involved in
melamine-related
kidney stone formation. Our findings are important for understanding pathogenesis of
melamine-related
kidney stone formation and estimating its clinical prognosis.