Melamine, powdered milk, and nephrolithiasis in Chinese infants.

Melamine, a synthetic nitrogenous product found in many industrial goods and even in fertilizer destined for use in growing crops for human consumption, was recently found to have been added to foods in China — including many different powdered infant formulas1 — to increase their measured, but not biologically available, protein content. Melamine is largely not degraded in humans, although several other compounds (ammeline, ammelide, and cyanuric acid) may become cocontaminants during the manufacturing process, and the main route of excretion after absorption from the gastrointestinal tract appears to be through the urine.2 The findings of acute kidney failure and symptomatic and asymptomatic kidney stones in infants and children previously exposed to melamine through the consumption of tainted powdered infant formulas have caused great concern. In this issue of the Journal, an original article by Guan et al. from Beijing3 and letters to the editor from Ho et al. from Hong Kong4 and Wang et al. from Taipei5 provide readers with substantial information about the relation between exposure to melamine-containing powdered infant formula and nephrolithiasis in infants and children. Observational data reported by these authors reveal an association between the prevalence of kidney stones as determined on ultrasonography of the kidney at one point in time and a history of melamine exposure based on the amounts in infant formulas as reported by the Chinese authorities. Guan et al. studied 589 children living in or near Beijing whose parents responded to the offer of a free screening; Wang et al. and Ho et al. studied 651 children residing in Taiwan and 2140 residing in Hong Kong, respectively, who underwent testing including ultrasonography of the kidneys. However, discrepancies in the numbers of exposed children in whom stones developed (and in the categories of exposure to melamine) are found when comparing the three reports. Kidney stones were seen in nearly 10% of the children studied in Beijing who received formula with a high melamine content (>500 ppm) or a moderate melamine content (<150 ppm), and slightly more than 20% of children residing in Taiwan and fed formula with a melamine content exceeding 2.5 ppm had stones. In contrast, only one child residing in Hong Kong and presumably exposed to melamine had a definite kidney stone. How can we best interpret such data to assess the risks for other infants and children who were fed these melamine-contaminated formulas? One way is to examine the number of people in whom stones would form in the absence of melamine exposure. The estimated number of adults in the United States between the ages of 20 and 74 years in whom stones developed was 5.2% from 1988 through 1994, an increase over the 3.8% from 1976 through 1980.6 There are no published incidences or prevalences for nephrolithiasis in children, but anecdotal discussions among experts suggest that such rates are currently increasing over those in past decades. In both children and adults, dietary and lifestyle factors appear to play an influential role in stone formation,7 albeit within a background of genetic susceptibility.8 Thus, Guan et al. and Wang et al. report prevalences that appear to be significantly higher than expected on the basis of data