title: Melamine Nephrotoxicity is Mediated by Hyperuricemia.
abstract: OBJECTIVE
  We tested whether melamine nephrotoxicity was exacerbated by urate (a typical component of renal stones in humans) in rats with hyperuricemiainduced by the uricase inhibitor, potassium oxonate (Oxo).
  
  
  METHODS
  Rats were exposed to melamine or Oxo alone or combinations of melamine (200-400 mg/kg) and Oxo (200-600 mg/kg) for 3 consecutive days. Kidney injury was evaluated by renal biochemical functions, histomorphology, and lipid peroxidation. Kidney crystals were analyzed for their composition.
  
  
  RESULTS
  Nephrotoxicity was minimal in animals administered melamine or Oxo alone, but it was demonstrable in animals administered at least 800 mg/kg of the two compounds combined. All rats in the 400+600 (melamine+Oxo) and 400+400 mg/kg groups and 4 out of 6 in the 200+600 mg/kg group died within 3 days; no rat died in the 200+400 or 200+200 mg/kg group. Dose-dependent renal damage resembling clinical findings in affected patients was observed in rats administered the two compounds. Crystal composition determination revealed the existence of melamine and uric acid in the affected kidneys, resembling human stones.
  
  
  CONCLUSIONS
  Our findings suggest that uric acid plays a key role in melamine-related kidney injury in humans. Future studies should consider uric acid together with melamine when examining adverse effects in humans.
authors.affiliation: Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health, Peking University Health Science Center, Beijing 100191, China; Department of Epidemiology and Health Statistics, School of Public Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Long
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Hong Tian
authors.initials: HT
authors.lastname: Li
authors.affiliation: Institute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Lin Lin
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Departments of Pediatrics, Environmental Medicine and Population Health, New York University School of Medicine, New York 10016, USA.
authors.forename: Howard
authors.initials: H
authors.lastname: Trachtman
authors.affiliation: Departments of Pediatrics, Environmental Medicine and Population Health, New York University School of Medicine, New York 10016, USA; NYU Wagner School of Public Service, New York 10012, USA; NYU Steinhardt School of Culture, Education and Human Development, New York 10003, USA.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Trasande
authors.affiliation: nstitute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Pei Xin
authors.initials: PX
authors.lastname: Wang
authors.affiliation: nstitute of Reproductive and Child Health/Ministry of Health Key Laboratory of Reproductive Health, Peking University Health Science Center, Beijing 100191, China; Department of Epidemiology and Health Statistics, School of Public Health, Peking University Health Science Center, Beijing 100191, China.
authors.forename: Jian Meng
authors.initials: JM
authors.lastname: Liu
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D033461:Hyperuricemia / Q000139:chemically induced / Q000150:complications*; D007674:Kidney Diseases / Q000139:chemically induced*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D010094:Oxonic Acid; D017208:Rats, Wistar; D014227:Triazines / Q000633:toxicity*
chemical_list: D014227:Triazines; C489337:potassium oxonate; D010094:Oxonic Acid; C011907:melamine
keywords: Hyperuricemia; Melamine; Nephrotoxicity; Urolithiasis