Outbreaks of Renal Failure Associated with Melamine and Cyanuric Acid in Dogs and Cats in 2004 and 2007

Abstract

Sixteen animals affected in 2 outbreaks of pet food-associated renal failure (2 dogs in 2004; 10 cats and 4 dogs in 2007) were evaluated for histopathologic, toxicologic, and clinicopathologic changes. All 16 animals had clinical and laboratory evidence of uremia, including anorexia, vomiting, lethargy, polyuria, azotemia, and hyperphosphatemia. Where measured, serum hepatic enzyme concentrations were normal in animals from both outbreaks. All animals died or were euthanized because of severe uremia. Distal tubular lesions were present in all 16 animals, and unique polarizable crystals with striations were present in distal tubules or collecting ducts in all animals. The proximal tubules were largely unaffected. Crystals and histologic appearance were identical in both outbreaks. A chronic pattern of histologic change, characterized by interstitial fibrosis and inflammation, was observed in some affected animals. Melamine and cyanuric acid were present in renal tissue from both outbreaks. These results indicate that the pet food-associated renal failure outbreaks in 2004 and 2007 share identical clinical, histologic, and toxicologic findings, providing compelling evidence that they share the same causation.

Biodegradation of melamine and its hydroxy derivatives by a bacterial consortium containing a novel Nocardioides species

“…For many years, melamine was considered to be a harmless substance unless administered as a large dose orally or intravenously (Lipschitz and Stokey 1945). However, this opinion of melamine changed after a large outbreak of nephrotoxic renal failure of dogs and cats associated with the intake of melaminecontaminated pet foods occurred in 2007 in North America (Brown et al 2007), and four thousand dogs and cats died from acute renal failure. Melamine and its hydroxyl analogues such as ammeline (4,6-diamino-2-hydroxy-1,3,5-triazine), ammelide (6-amino-2,4-dihydroxy-1,3,5-triazine), and cyanuric acid (1,3,5-triazinane-2,4,6-trione) were detected in vegetable proteins in the contaminated pet foods (Dobson et al 2008).…”

Melamine Toxicity

“…Cyanuric acid and the other MRCs ammeline and ammelide may be by-products when melamine is formed [19]. Melamine is high in nitrogen and allegedly was added to animal feeds to increase the apparent protein content in assays that measure nitrogen as a surrogate for protein content [1,2]. In the tainting of Chinese infant formula, melamine, without cyanuric acid, may have been added to compensate for intentional dilution (to increase saleable amounts) of the market-bound products [13,14].…”

“…Melamine was later implicated as the source of the outbreak [1]. In the USA during early 2007, the Food and Drug Administration (FDA) recalled certain pet foods after they caused many dogs and cats to become sick or die after developing urinary crystals.…”

“…In the USA during early 2007, the Food and Drug Administration (FDA) recalled certain pet foods after they caused many dogs and cats to become sick or die after developing urinary crystals. More than 100 potentially contaminated products were recalled [1][2][3]. Contaminated vegetable protein products imported from China were sold as "wheat gluten" and used as ingredients in pet foods.…”

“…This incident also reinforces Paracelsus' famous caveat, "the dose makes the poison," in that neither significant exposure nor toxicity would have been foreseen from common melamine exposure. For example, in 2004 and 2007, outbreaks of crystalluria and death in animals were caused by contamination of animal feeds with a combination of the stoneforming synergists melamine and cyanuric acid [1][2][3]. Early animal studies had shown stone formation and bladder carcinogenicity at high doses of melamine [4][5][6][7][8][9].…”