Abstract 16250: Melamine Impairs Renal and Vascular Function in Rats

Abstract

Introduction: Recent outbreak and consequence of nephrotoxicity and kidney stone in infants previously exposed to melamine-contaminated milk products is unprecedentedly grave as little is actually unknown about the mechanistic process leading to pathophysiological alterations in renal function in affected children. Hypothesis: The present study investigates whether neonatal ingestion of melamine leads to renal and vascular dysfunction in adulthood; and whether ingestion of melamine in pregnant rats leads to renal dysfunction in their offspring.

Methods: A combination of approaches were employed including functional examination on vascular reactivity in isolated rat renal arteries, renal blood flow measurement by functional magnetic resonance imaging technique, assay for pro-inflammatory and fibrotic biomarkers, immunohistochemistry, and biochemical measurements of plasma and renal melamine.

Results: We provide novel mechanistic evidence demonstrating for the first time that melamine significantly reduces renal blood flow and impairs renal and vascular function associated with over-expression of pro-inflammatory markers, transforming growth factor-β1 (TGF-β1), bone morphogenic protein 4 (BMP4) and cyclooxygenase-2 (COX-2) in renal vasculature and kidney. Melamine also induces renal fibrosis and inflammatory changes. The present study provides scientific evidence revealing part of mechanisms by which melamine causes nephropathies in neonatal animals and impact on postnatal animals resulting from exposure to melamine during pregnancy.

Conclusions: We provide evidences supporting recent clinical observations of kidney stone and acute renal failure in infants consuming melamine-contaminated milk products and the possible mechanisms involved.