Diagnosis and spectrum of melamine-related renal disease: Plausible mechanism of stone formation in humans

Background: An epidemic of urinary stones affecting children after consumption of melamine tainted milk is unfolding. We defined clinicopathological features of the disease for diagnosis, monitoring, and treatment of this group of patients. Methods: A clinicopathological study on exposed children with ultrasonographic evidence of urolithiasis was conducted. Melamine and cyanuric acid levels in the urine were determined by mass spectrometry. Results: Disease severity varied from acute renal failure with hydronephrosis to symptomatic or asymptomatic stones with or without abnormal urinalysis. All cases were aged < 3 y with > 50% cases having predisposing urinary metabolic risk factors for urolithiasis. Most of the stones were located in the renal pelvis and measured 2.5-18 mm by ultrasonography. We found a strong correlation between renal stone size and urinary melamine concentration. For stones < 10 mm, a 10 μg/mmol creatinine increase in urinary melamine concentration is associated with approximately 1 mm increase in the size of the stone. The high degree of correlation strongly suggests that melamine is related to stone formation in humans. Using ROC analysis, we propose that patients who have a persistent melamine level above the optimal cut-off value of 7.1 μg melamine/mmol creatinine in urine might have a significant exposure of melamine-tainted products. Unlike melamine, urinary cyanuric acid is not significantly different between cases and controls. Pathophysiological findings from feeding animals with melamine and cyanuric acid may not be directly applicable to humans. Conclusion: Both melamine and urine metabolic lithogenic factors are important for the formation of melamine-related stones. Apart from aiding with case screening and confirmation, the urine melamine level might as well be an indicator of residual melamine load in the body and thus is useful for following-up and monitoring of the confirmed cases. As the stones are small and can be passed out spontaneously, follow-up of these patients with urine melamine will be a convenient tool for monitoring the melamine load of the patients.