Long-term follow-up of nephrotoxicity in rats administered both melamine and cyanuric acid

BACKGROUND: Melamine was recently identified as a risk factor for renal calculi following the milk powder contamination in China. However, the long-term natural history of melamine exposure and its renal effects remain unknown. We evaluated renal function and other adverse health effects using a rat model administered melamine and cyanuric aid, considering age and sex. METHODS: Twelve male F334/N rats each of ages 6, 10, and 26 weeks (N = 36) were equally assigned to Group M + C or controls. Group M + C rats were administered 12 mg · kg(-1) · day(-1) of melamine and cyanuric acid for 28 days. Serum and urine samples and kidney sections were evaluated on day 28. Six-week-old male and female F344/N rats were administered 12 mg of melamine and cyanuric acid for 28 days. Body weights were measured weekly; on days 0, 28, 90, and 180 after the 28-day period of melamine and cyanuric acid administration, serum samples and kidney sections were obtained. RESULTS: Although the control group had no crystals, 6-week-old Group M + C rats had more crystals compared to the 10- and 26-week old Group M + C rats. Male rats also had significantly more crystals than females of the same age. Male rats were affected to a greater extent than females. CONCLUSION: Younger rats experienced more severe renal failure and greater renal crystal deposition following melamine and cyanuric acid administration. However, after melamine and cyanuric acid administration cessation, crystal deposition and renal failure improved and did not cause growth arrest. Therefore, early diagnosis of melamine-associated calculi is critical.