Melamine in milk linked to kidney disease in children

NEW YORK (Reuters Health) - A study of kidney disease risk in Chinese children who were exposed to milk contaminated with melamine is being published in The New England Journal of Medicine. It shows that exposure to melamine-contaminated powdered formula increased the risk of urinary stones by up to sevenfold, but the clinical relevance of these stones, which often produce no symptoms or laboratory abnormalities, is unclear.

Melamine is a colorless, crystalline organic compound that is rich in nitrogen. It is widely used in the manufacturing of materials such as plastics, adhesives, countertops, and dish ware.

In China, where the contamination occurred, water was added to raw milk to increase its volume. As a result of this dilution, the milk had a lower protein concentration.

Companies using the milk for further production, such as powdered infant formula, normally check the protein level through a test measuring nitrogen content. The addition of melamine increases the nitrogen content of the milk and therefore it appears to have a higher protein content than it actual.

The addition of melamine into food is not approved by the FAO/WHO Codex Alimentarius (food standard commission), or by any national authorities.

While there are no direct human studies on the effects of melamine, data from animal studies showed that melamine caused bladder stones.

When combined with cyanuric acid, which may also be present in melamine powder, melamine can form crystals that can give rise to kidney stones. These small crystals can also block the small tubes in the kidney potentially stopping the production of urine, causing kidney failure and, in some cases, death.

Melamine has also been shown to have carcinogenic effects in animals in certain circumstances, but there are insufficient data to make a judgment on carcinogenic risk in humans.

A jump in the rates of urolithiasis, the formation of stones in the kidney, bladder and urinary tract, among young children occurred in China last year. The government announced in September that the epidemic was most likely due to melamine contamination of powdered-milk formula.

In their study, Dr. Jie Ding, from Peking University First Hospital, and colleagues describe the investigation that ultimately linked melamine exposure to urolithiasis in young children. The study involved a parental survey for 589 children, 36 months of age or younger, who were being screened for melamine exposure and symptoms of urinary tract stones. Standard urinary function tests as well as ultrasonography were also performed.

Overall, 421 children consumed melamine-tainted formula. Fifty children had confirmed stones, including 8 children without melamine exposure, 112 had suspected stones, and 427 had no stones.

Blood and white blood cells were seen in the urine of 5.9 percent and 2.9 percent of children with stones, respectively, which is comparable to the rates seen in children without stones.

Moreover, blood levels of creatinine, urea nitrogen, and alanine aminotransferase were usually normal in the patients with stones. Only 4 of 41 patients with stones had urinary markers suggesting glomerular dysfunction.

Children exposed to formulas with high-melamine content (>500 ppm) were 7.0 times more likely to have urinary stones than those given formulas not tainted with melamine. Preterm infants were 4.5-times more likely to have stones than their full-term peers.

In related correspondence, a group from the Chinese University of Hong Kong report that of 2,140 children who underwent ultrasound screening from September 28 to October 17, 2008, just one was found to have urolithiasis. Some other abnormalities were noted in a few children, but their clinical significance, if any, is unclear, they add.

According to a related editorial, the American Society of Pediatric Nephrology advises a conservative approach for treating asymptomatic infants, “since stones presumed to have been induced by melamine appear to be passed easily after hydration” and because long-term follow-up data are lacking.

Ultrasound testing of all potentially exposed Chinese children who are now living in the U.S. is unlikely to be cost effective, editorialist Dr. Craig B. Langman, from Northwestern University, Chicago, comments.

SOURCE: The New England Journal of Medicine, Online First February 4, 2009.