Thr NEW ENGLAND JOURNAL f MEDICINE Table 3.Laboratory Results in the Children Studied,Ac ording to the Presence or Absence ofUrinary Tract Stones Group Hematuria umber/total mber (pern) Children with stones 2/34(5.9) 1/342.9 0/34 4/41(9.8) 0/41 higonhsupead 0/76 1/761.3) 1/76(13 12/88(13.6) 4/884.5) without stone 4126215) 4/2621.5 22620.8 15/269(5.6 8/269(3.0 All children 6/372(1.6 63721.6 3/372(0.8 31/398(78) 12/3983.0 P value 0.10 0.63 0.65 0.04 0,42 s of children with the use of Fisher's exact test.except in the case the diagnosis of melamine-related urinary stones of bion an ultr Unlike typical urinary tract stones.most of the lar dysfunction,but not renal tubular dysfunc melamine-associated stones we detected were not tion,differed significantly among children who characterized by shadowing on ultrasonography. had stones,those who were suspected to have ens of melamin nes,and those who did not have stones.More sto n with renal fa d to h es ha using li nass spe nd tha 13 posed primarily of uric acid and melamine e.Before were no significant differences in the incidenc the announcement of formula contamination. of glomerular dysfunction between children with a 3-month-old boy was admitted to our hospita stones and those without stones (9.8%and 5.6% after presenting with a 2-week history of diarr P=0.37).It is unclear whether th re were other On ultr hhogapmutpe e tiny stones,the larg acto t play,such as othe r renal diseases,among were of to have sto tion of the othe the announcement of melamine contamination studv.se we inquired about exposure to melamine:the boy normal in all but two children,both under 1 yea melamine for 3 months atment have st h included hydration and a ther child nelamine form (0.u in dia Th ry tract in enal nelvis This case s ests that mel e not det ermined related stones may not be dense and may be eas In our study,121 children were exposed to ily passed after hydration and alkalinization find high-melamine formula.but only 23 of these chil ings that are consistent with a urate component Iren had urinary stones.Thu urinary stone Mos ciated sto our se loped in a minority of ch dren wer san ith th nosed to mel indicated that contaminated pet food ter it is not knowr times as likely as term infants to have stones whether melamine or uric acid mixed with mela Gilsanz et al.s reported that preterm infants were mine forms microcrystals that could cause tubu- more susceptible than term infants to the devel lointerstitial injury in humans opment of urinary stones not related to melamine 1072 N ENGLJ MED 360:11 NEJM.ORG MARCH 12,2006 Downloaded from nejm. n Oc r18,2011.FoThe new england journal o f medicine 1072 n engl j med 360;11 nejm.org march 12, 2009 the diagnosis of melamine-related urinary stones requires an ultrasonographic examination. Unlike typical urinary tract stones, most of the melamine-associated stones we detected were not characterized by shadowing on ultrasonography. Sun et al.4 analyzed specimens of melamine-asso￾ciated stones from 13 children with renal failure by using liquid chromatography–mass spectropho￾tometry and found that the stones were com￾posed primarily of uric acid and melamine. Before the announcement of formula contamination, a 3-month-old boy was admitted to our hospital after presenting with a 2-week history of diarrhea. On ultrasonography, multiple tiny stones, the larg￾est of which was 0.3 cm by 0.4 cm, were observed bilaterally in the renal pelvis, without shadowing or obstruction of the urinary tract system. After the announcement of melamine contamination, we inquired about exposure to melamine; the boy had received formula containing 150 ppm of melamine for 3 months. After treatment for 9 days, which included hydration and urine alka￾linization, ultrasonography was repeated. Only one stone (0.5 cm in diameter) was detected in his left renal pelvis. This case suggests that melamine￾related stones may not be dense and may be eas￾ily passed after hydration and alkalinization, find￾ings that are consistent with a urate component. Most melamine-associated stones in our series were small and sand-like, especially those in the renal pelvis. A previous study showed renal tu￾bular degeneration in dogs exposed to melamine￾contaminated pet food.1 However, it is not known whether melamine or uric acid mixed with mela￾mine forms microcrystals that could cause tubu￾lointerstitial injury in humans. In our analysis of biomarkers of early renal injury in 398 children, the incidence of glomeru￾lar dysfunction, but not renal tubular dysfunc￾tion, differed significantly among children who had stones, those who were suspected to have stones, and those who did not have stones. More children suspected to have stones had apparent glomerular dysfunction than those who did not have stones (13.6% vs. 5.6%, P=0.01), yet there were no significant differences in the incidence of glomerular dysfunction between children with stones and those without stones (9.8% and 5.6%, P=0.37). It is unclear whether there were other factors at play, such as other renal diseases, among the children suspected to have stones. Whether melamine can cause injury of other tissues and organs in humans is unknown. In our study, serum alanine aminotransferase levels were normal in all but two children, both under 1 year of age; one of the two children was suspected to have stones and the other did not have them. Nei￾ther child had received high-melamine formula, and neither had symptoms of urinary tract infec￾tion. The reasons for the increased serum alanine aminotransferase levels were not determined. In our study, 121 children were exposed to high-melamine formula, but only 23 of these chil￾dren had urinary stones. Thus, urinary stones developed in a minority of children exposed to high-melamine formula. Multivariate logistic￾regression analysis with the use of two models indicated that preterm infants were 3.7 to 4.5 times as likely as term infants to have stones. Gilsanz et al.5 reported that preterm infants were more susceptible than term infants to the devel￾opment of urinary stones not related to melamine, Table 3. Laboratory Results in the Children Studied, According to the Presence or Absence of Urinary Tract Stones. Group Hematuria Leukocyturia Proteinuria Glomerular Dysfunction Renal Tubular Dysfunction number/total number (percent) Children with stones 2/34 (5.9) 1/34 (2.9) 0/34 4/41 (9.8) 0/41 Children with suspected stones 0/76 1/76 (1.3) 1/76 (1.3) 12/88 (13.6) 4/88 (4.5) Children without stones 4/262 (1.5) 4/262 (1.5) 2/262 (0.8) 15/269 (5.6) 8/269 (3.0) All children 6/372 (1.6) 6/372 (1.6) 3/372 (0.8) 31/398 (7.8) 12/398 (3.0) P value* 0.10 0.63 0.65 0.04 0.42 * P values were calculated for the comparisons among the three subgroups of children with the use of Fisher’s exact test, except in the case of glomerular dysfunction, for which Pearson’s chi-square test was used. The New England Journal of Medicine Downloaded from nejm.org on October 18, 2011. For personal use only. No other uses without permission. Copyright © 2009 Massachusetts Medical Society. All rights reserved