| Background:In September 2008, China reported an epidemic of urinary stones in infants fed with melamine-contaminated milk powder. In less than two months,294,000 cases of melamine-associated kidney stones were reported, with over 51,900 babies and infants were hospitalized. Overall, at least six confirmed deaths were linked to consumption of melamine-tainted powdered milk formula. Renal disorders and renal calculi in asymptomatic children were detected by ultrasonic screening.Objective:We investigate causes of urinary stone sudden increase in infants and to prevent more occurrence of urinary stone. We also investigate the risk factors of melamine associated urolithiasis. After treatment, most children with melamine-induced urolithiasis were cured and discharged. We retrospectively analyzed the clinical features and therapeutic efficacy in chidren with urolithiasis caused by ingestion of melamine-contaminated infant formula, as well as identified the risk factors for occurrence of acute kidney injury (AKI). Also, we performed a study to investigate the rehabilitated condition, renal glomerular and tubular dysfunction of patients with melamine-induced urolithiasis at one-year follow-up. And we analyzed and evaluated long-term efficacy of treatment in young children with acute kidney injury (AKI) caused by melamine-contaminated infant formula.Methods:The clinical data of 22 infants with urinary stones visiting clinic of second hospital of Lanzhou university from April 2008 to September were analyzed retrospectively. Also the detailed data of infant and young children screened for urolithiasis from of September 14, 2008 to January 6,2009 were analysis retrospectively. According to the case:control ratios of 1:1, we selected the control group from those without urolithiasis randomly. Univariate and multivariate analysis were performed with a logistic regression model to assess for independent risk factors for urolithiasis. A total of 619 children with melamine-induced urolithiasis were admitted into 20 different hospitals in Gansu province, China. Their clinical and laboratory datas, ultrasonograms, and treatment methods were retrospective recorded and analyzed. Univariate and multivariate analysis were performed with a logistic regression model to assess for independent risk factors for occurrence of acute kidney injury (AKI). We followed up young children with melamine-induced urolithiasis from September to December 2009, which included urinalysis, renal-function tests, urinary tests for biochemical markers of renal glomerular and tubular function, and ultrasonography. Also, we retrospectively analyzed clinical and laboratory data, ultrasonograms and treatment methods in infant patients with melamine-induced urolithiasis and AKI who were hospitalized in Gansu Province, China. Patients were monitored postoperatively with data from ultrasonography, urinalysis, blood and urine biochemistry. We followed up the children suffering from melamine-induced urolithiasis and AKI from March to May 2010.Results:22 infants with urinary stones were bottle feeding or mixed feeding, and all infants were in the process of consumption of sanlu powdered infant milk formulas.13 cases have upper respiratory tract infection or diarrhea history before presenting urination symptoms, accounting for 59.09%. Of the screened children,647 included in stones group and 647 in control group. There were 678 boys and 616 girls with an average age of 19.27 months. Logistic regression analysis shows that the children fed with sanlu powdered infant milk formula were 6.09 times more likely to have stones (P<0.01) than those with other melamine-contaminated formula. Boys were 1.39 times more likely to have stones (P<0.01) than girls. Children fed with formula alone were 1.61 times more likely to have stones (P<0.01) than those with formula and breast milk. Long duration of formula feeding and younger children were the risk factors for melamine associated urolithiasis (P<0.05, respectively). The children aged less than 6 months,6 to 12 months,12 to 24 months were 5.23 (P<0.01),2.73 (P<0.01),1.60 (P<0.01) times more likely to have stones than those more than 24 months. The time of formula feeding 3 to 6 months,6 to 12 months and more than or equal to 12 months were 2.10 (P<0.01),2.81 (P<0.01),4.75 (P<0.01) times more likely to have stones than those less than 3 months. Among the 619 children,408 were boys and 211 girls with age ranging from 1 month to 88 months (mean age,16.32 months).520 children (84.0%) were asymptomatic and detect by ultrasound screening program.117 (18.9%) children had co-existent renal, ureteral, bladder or/and urethral stones (stones at more than 1 site). 577 patients received conservative treatment and 454 become stone-free (78.7%). Of the 151 patients with renal and/or ureteral stones,1 to 6 session Extracorporeal Shock Wave Lithotripsy (ESWL) were performed in 81 patients (61 successes in 172 treatments, Cumulative success rate, 35.5%), retrograde ureteral catheterization (UC) in 70 patients (56 patients were successfully treated,80.0%). In centers without expertise in minimally-invasive medical technique,5 patients with bilateral obstructive renal failure were successfully treated with Ureterolithotomy (ULT,4) and percutaneous nephrostomy (PCNL,1). For the remaining 27 children with refractory renal or ureter stones,9 were successfully treated with percutaneous nephrolithotomy (PCNL) and 18 children underwent ureteroscopic lithotripsy to become stone-free. A total of 22 bladder and/or urethral stones were successfully treated with cystoscopic (Cys L) or urethroscopic lithotripsy. Logistic regression analysis reveal that the children fed with sanlu powdered infant milk formula were 19.73 times more likely to occurrence of AKI than those with other formula. A significantly higher number of patients occurrence of acute kidney injury (AKI) among children aged 6 to 11 months (OR,9.59, P<0.01) and 12 to 17 months(OR,5.06, P<0.01). The children with any one symptoms of upper respiratory tract infection, diarrhea, dehydration, and fever (OR,4.29, P<0.01) remained independent risk factor for occurrence of AKI by multivariate analysis.81 children with detailed data were enrolled and followed up one year late.51 were male and 30 female, with a mean age of 25.53±7.91 months (range 13-48 months). According to different treatment,81 children were divided into two groups. Group 1 was conservative treatment group (n=54) and group 2 was intervention treatment group (n=27). In Group 1, the outcomes of 3 (5.6%) children have stone-residual:one girl has calculus of 0.4 cm in diameter in the left kidney and two girls have calculus of 0.3 cm in diameter in the right kidney. In Group 2, the outcomes of 2 (7.4%) children have stone-residual, one boy has crystallization of 0.23 cm in diameter in the right kidney, one boy has calculus of 1.5 cm in diameter in the left kidney, positive stone was confirmed by X-ray and accepted percutaneous nephrolithotomy. Urinary microalbumin levels were significantly increased in children with melamine-induced urolithiasis compared with the normal control group (P<0.01). And the incidence of glomerular dysfunction (UMA more than 19μg/ml) among children with melamine-induced urolithiasis, was significantly increased compared with control group (P=0.03). Blood urea nitrogen and serum creatinine were within the normal range and these is not any significant difference between two groups. A total of 47 children with melamine-induced urolithiasis and AKI was hospitalized in 7 institutions. The mean age was 10 months (mean±SD,10.83±5.11 months). Thirty-four (72.34%) were male. Calculi size ranged from 3 to 14 mm in diameter. Nine patients (19.15%) were successfully treated with conservative treatment; 32 (68.09%) underwent retrograde ureteral catheterization and 8 had simultaneous cystoscopic or urethroscopic lithotripsy; Four were successfully treated with ureterolithotomy, and 1 underwent percutaneous nephrostomy. Thirty-eight patients were followed up for a mean±SD of 18.50±5.27 months and their renal functions were found to have completely recovered. Five (13.16%) cases had residual renal stones with diameter ranged from 2 to 4 mm.Conclusion:The epidemic of urinary stones in infants were related to exposure to melamine-tainted sanlu powdered infant milk formulas. Upper respiratory tract infection or diarrhea most likely induce urinary stones formation and obstructive anuria in infants. We confirmed that the children fed with high melamine infant formula (sanlu powdered infant milk formula), boy, children fed with formula alone were risk factors of melamine associated urolithiasis. We also found the risk for melamine associated urolithiasis decreased with age, and increased with time of formula feeding. Most children with melamine-induced urolithiasis were treated successfully with infusion of fluids, urine basification and diuresis. ESWL is a safe and effective technique for cases where conservative treatment fails. Fed with sanlu powdered infant milk formula and children with any one symptoms of upper respiratory tract infection, diarrhea, dehydration, and fever were risk factors for occurrence of acute kidney injury (AKI) in children with melamine-induced urolithiasis. We also found that children aged 6 to 11 monthsn and 12 to 17 months more prone to developed AKI. By now (1 year follow-up) the patients with stone-residual>10 mm, surgery been recommend. Melamine-induced urolithiasis could lead to AKI. Removing obstruction promptly by surgical intervention has been found to be effective with satisfactory outcomes observed at mean follow-up period of 18-month. However, residual renal stone remained in 13.16% of the cases which required continued close observation. |
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