Melamine-related kidney stones and renal toxicity.

Several well-documented outbreaks of melamine poisoning have occurred in both animals and humans during the past 7 years, which led to the identification of melamine and cyanuric acid as nephrotoxins. This Review provides an overview of the known experimental and observational data (including toxicology, epidemiology, and pathology) concerning melamine contamination of foodstuffs, both alone and in combination with cyanuric acid. The various renal effects of ingestion of these compounds in both animals and humans are described, and a hypothesis on the mechanism of formation of melamine-based kidney stones is presented. Finally, the public health measures taken in the wake of the melamine contamination events are discussed.

Melamine-tainted milk product-associated urinary stones in children.

BACKGROUND: An outbreak of urinary stones related to consumption of melamine-tainted milk products (MTMP) occurred in China in 2008. The aim of the present study was to evaluate such children to identify their clinical features and risk factors. METHODS: Renal ultrasound was performed for 7328 children who presented to a Sichuan teaching hospital between 13 September and 15 October 2008 due to concern of such stones. Clinical data, family information, feeding history and urinary stones were analyzed. RESULTS: Of the 7328 children, 189 (2.58%) had ultrasound findings of urinary stones, and 51 were admitted. Age (mean ± SD) was 27.4 ± 25.5 months, and 101 were male and 88, female. The odds ratio (OR) for urinary stones for infants and young children (1-3 years) as compared to older children (>3 years), was 2.42 (95% confidence interval [CI], 1.64-3.56; P < 0.0001) and 1.95 (95%CI, 1.31-2.89; P < 0.0011), respectively. Independent risk factors associated with urinary stones included consumption of MTMP with melamine at > 5500 mg/kg (OR, 13.3; 95%CI, 6.8-26.1, P < 0.0001) as compared to that with melamine at < 200 mg/kg, and younger father (P = 0.0006). On logistic regression, the only risk factor associated with inpatient care was lower family income per person (OR, 4.4; 95%CI, 1.2-15.9, P = 0.02). Repeat ultrasound for 51 children at mean follow up of 15.3 ± 8.9 days found that 33 passed out all stones, which was associated with a larger number of smaller stones (P = 0.003). Urinary stones contained melamine and uric acid, but no cyanuric acid. CONCLUSIONS: MTMP-associated urinary stones were more frequent in young children and more severe in children from poorer families.

Melamine toxicity.

Melamine contamination of infant formula in China and its health effects highlight the safety of the global food supply especially as it relates to formula-fed infants. Melamine is a widely used industrial chemical not considered acutely toxic with a high LD(50) in animals. The data available on acute and chronic human exposure to melamine have been limited and extrapolated from animal data. Pet food contamination in 2004 and 2007 showed stone formation and illness in animals when melamine was co-ingested with cyanuric acid. The recent outbreak in infants showed that melamine ingested in large doses may cause stones and illness without significant ingestion of cyanuric acid or other melamine-related chemicals. This may be due to increased uric acid excretion in infants and formation of melamine-uric acid stones. Diagnosis and treatment of infants exposed to melamine requires further study. Clinical signs and symptoms in infants are nonspecific. The stones may be radiolucent and are not consistently seen on ultrasound. The use of alkalinization of the urine for treatment has been proposed, but is of unproven benefit. The FDA and other regulatory agencies have recommended acceptable levels of melamine in foods for consumption. Melamine ingestion has been implicated in stone formation when co-ingested with cyanuric acid, but will cause urinary stones in infants when large amounts of melamine alone are ingested.

Ultrasonographic characteristics of urolithiasis in children exposed to melamine-tainted powdered formula.

BACKGROUND: Since the outbreak of renal diseases among children who had consumed melamine-tainted powdered formula in 2008, urinary system ultrasound examination was carried out for these children at our hospital. This study aimed to investigate the ultrasonographic characteristics of urolithiasis caused by melamine-tainted powdered formula. METHODS: From September 12 to October 9, 2008, urinary system ultrasound examination for children after consumption of melamine-tainted powdered formula was carried out at the Children's Hospital of Zhejiang University, China. A total of 15,577 infants and children were subjected to the examination. A questionnaire with items including demographic characteristics, history of exposure and clinical symptoms were completed before examination. RESULTS: Among the 15,577 children, 7988 were boys and 7,589 girls with age ranging from 1 month to 15 years (mean age, 22 months). Urolithiasis was found in 562 patients with an identification rate of 3.6%. Urolithiasis was identified mainly in the children aged 36 months or younger (88.6%). Unilateral kidney calculi were found in 431 children and bilateral kidney calculi in 131 children. Eleven of these children also had ureteric calculi, 1 had bladder calculi, 2 had urethral calculi, and 2 had gallbladder calculi. Fifteen children had urinary tract obstruction. Ultrasonographic characteristics of these melamine calculi were different from the calcium oxalate calculi, i.e., the lesions were less echogenic, had a more "sandy" appearance and were less dense. The posterior portion of the calculi could be observed and was accompanied with a feeble or absent acoustic shadow. CONCLUSIONS: Melamine-induced calculi were ultrasonographically less echogenic, sand-like and discrete; the posterior portion of the calculi was accompanied with a feeble or absent acoustic shadow. It might be a new type of urolithiasis in children.

Mutagenicity study of workers employed in the styrene and polystyrene processing and manufacturing industry.

Mutagenicity studies were undertaken on lymphocytes from the following groups of persons exposed to styrene or polystyrene: one group from a styrene manufacturing plant, one from a polystyrene plant, and three from plants processing unsaturated polyester resins with different manufacturing methods. For all the groups the concentration of styrene in the atmosphere of the workplace was measured at various points and the amount of urinary mandelic acid was determined. In each case 100 metaphases were analyzed for chromosomal aberrations. The results were compared with reference groups.

Airway disease caused by phenolic (phenol-formaldehyde) resin exposure.

A standardized respiratory questionnaire and pulmonary function tests, including measurement of forced vital capacity (FVC), one-second forced expiratory volume (FEV1.0), and maximum expiratory flow rate at 50% FVC (MEF50%), were administered to five groups of employees in a filter-manufacturing plant to determine the acute and chronic effects of exposure to phenolic resin fumes. Employees exposed for more than five years had lower FEV1.0/FVC and MEF50%/FVC ratios than a group that had smoked more but that had never been consistently exposed to resin fumes. The existence of chronic airway obstruction was also evident by a slight excess of chronic cough and sputum production in the exposed groups. However, in spite of the high proportions of subjects reporting acute respiratory symptoms, we found only small decreased in pulmonary function during the workday and workweek.