Melamine and the Kidneys: Understanding the Toxic Connection

Melamine is an important and widely used organic industrial chemical. Recently, clinical findings of renal failures and renal calculi in infants have been associated with the ingestion of melamine-contaminated infant formula. Melamine is also present in plastic materials which are widely used in the world. The toxicity of melamine caught the attention of physicians as a result of a recent spate of renal injury after exposure to melamine-tainted milk. Melamine is an organic nitrogenous compound used in the production of plastics, dyes, fertilizers, and fabrics. In the current incident, melamine was added to milk to elevate false assay results for protein content. A variety of toxic effects from melamine, include nephrolithiasis, chronic kidney inflammation, and bladder carcinoma.

The mechanism of melamine nephrotoxicity is still unknown, but clues are available from animal studies. Melamine is rapidly excreted in the urine (90% of the administered dose in 24 h), but melamine can precipitate in distal renal tubules. Histopathologic specimens from affected cats and dogs from the 2004 and 2007 outbreaks show characteristic intratubular green radial crystals and crystalluria. The morphology and histochemical staining pattern are distinct from calcium oxalate or calcium phosphate crystals. Some affected animals suffered from acute kidney injury (AKI), whereas others developed chronic kidney disease (CKD). Melamine-associated AKI in animals was characterized by necrosis of distal tubular cells and mild inflammation. Chronic toxicity showed larger crystals, interstitial inflammation, and fibrosis. 

Melamine and related amine analogs have natriuretic properties in dogs at a dose of 125mg/kg, and thus, may exacerbate AKI by leading to pre-renal azotemia in susceptible animals or individuals. The nitrogen content of melamine is unlikely to artificially increase the blood urea nitrogen (and thus feign AKI) because, in autopsy studies, detection of melamine in diseased renal tissue occurred in the absence of melamine metabolites.

Currently, various medicinal plant extracts and compounds are tested for anti-melamine-induced renal calculi. Moreover, the molecular mechanisms of the treatment will also be investigated using different molecular techniques.

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