Melamine-associated Kidney Stone Formation Is Related To Renal Tubular Epithelial Cell Injury,Apoptosis And Inflammation

PURPOSE:To understand pathogenesis of melamine-associated kidney stone formation,we investigated in vivo the characterization of renal tubular cell under exposure to melamine and cyanuric acid.MATERIALS AND METHODS: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(HE),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.Apoptotic cells were examined by TUNEL assay.RESULTS:Melamine-associated crystals formed in glomerulus and wide renal tubue segment including proximal convoluted renal tubule(PCT),distal convoluted renal tubules(DCT),the limb loops of Henle and medullary collecting ducts(MCD)in the cortex and medulla.Crystals lead to tubular lumen dilatation and tubular epithelial cell necrosis under light microscopy.Renal tubular epithelial cells were observed that nucleus became irregular outlines and condensed,lysosomal-related structures increased,and integrality of renal tubule was deficient result from epithelial cells disintegration under electron microscopy.Apoptosis was noted widely in cortex and medulla and MCP-1 mRNA expression was significantly increased in the treatment group.CONCLUSIONS:Melamine-associated kidney stone formation is related to renal tubular epithelial cell injury,apoptosis and inflammation.Our findings are important for understanding pathogenesis of melamine-associated kidney stone formation and estimating its clinical prognosis.