title: Diagnosis and spectrum of melamine-related renal disease: plausible mechanism of stone formation in humans.
abstract: 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 microg/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 microg 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China. ching-wanlam@pathology.hku.hk
authors.forename: Ching-Wan
authors.initials: CW
authors.lastname: Lam
authors.forename: Lawrence
authors.initials: L
authors.lastname: Lan
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Che
authors.forename: Sidney
authors.initials: S
authors.lastname: Tam
authors.forename: Samson Sai-Yin
authors.initials: SS
authors.lastname: Wong
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Tao
authors.forename: Xiao-Ming
authors.initials: XM
authors.lastname: Tang
authors.forename: Kwok-Yung
authors.initials: KY
authors.lastname: Yuen
authors.forename: Paul Kwong-Hang
authors.initials: PK
authors.lastname: Tam
mesh_terms: D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007669:Kidney Calculi / Q000453:epidemiology / Q000378:metabolism* / Q000652:urine*; D008297:Male; D014227:Triazines / Q000008:administration & dosage / Q000378:metabolism* / Q000652:urine*
chemical_list: D014227:Triazines; C004632:cyanuric acid; C011907:melamine