Renal stone formation and
renal failure among Chinese infants administered
melamine-containing formula were increasingly reported in 2008. We investigated the mechanism by which
melamine and
cyanuric acid induce renal stone formation and
renal failure. Ten-week-old rats were administered either
melamine [2.4, 24, or 240 mg/kg/day], both
melamine and
cyanuric acid [each at 1.2, 12, or 120 mg/kg/day], or water (controls). Blood and 24-h urine samples and kidney sections were evaluated on days 3, 7, and 14. In rats administered
melamine alone or the low-dose
melamine/
cyanuric acid combination [1.2 mg/kg/day], crystals were not detected. On day 3, crystal formation was observed in the renal distal tubular lumens and collecting ducts of rats administered the intermediate-dose
melamine/
cyanuric acid [12 mg/kg/day], and the number of crystals increased during the course of the experiment. In rats administered the high-dose
melamine/
cyanuric acid [120 mg/kg/day], crystals were found in the proximal tubular lumens of the renal cortex on day 3, but
acute renal failure resulted in death by day 7. Polarized light optical microphotography and scanning electron microscopy revealed tubular lumens occluded by a layer of axle-shaped crystals. X-ray diffraction findings revealed a
nitrogen component but no
calcium. The upper regions of occluded tubes were expanded, and the epithelium was thin.
Melamine and
cyanuric acid in combination, but not by
melamine alone induce crystal formation and affected renal functioning.
Renal failure due to
melamine cyanurate crystals appears to occur via tubular occlusion.