| Summary: | 博士 === 高雄醫學大學 === 職業安全衛生研究所 === 98 === Background and objective: The outbreak of melamine-tainted infant formula has raised concerns about causing kidney stones and adverse renal outcomes in young children worldwide, particularly in China, Hong Kong, and Taiwan. However, it is not known whether exposure to melamine might also cause urolithiasis in adults. In Taiwan, the prevalence rate of adult urolithiasis is relatively high (~9.6%), due to its high occurrence and recurrence rate of urolithiasis, burden of medical expenditure is expected to be large. This study aims to investigate the association between urinary melamine concentration and the risk of urolithiasis in adults in Taiwan.
Materials and methods: This study was designed as a hospital-based case-control study. Between 2003-2007, patients with urolithiasis were enrolled from Kaohsiung Medical University Hospital (KMUH) and Kaohsiung Municipal Hsiao-Kang Hospital. Their stone specimens were confirmed to have uric acid and calcium stones components by infrared spectroscopy analysis (FTIR). For comparison, sex- and age- matched subjects were randomly selected from people receiving general health examinations at KMUH during the same period. The controls reported no past history of stone disease or clinical findings of stones, which was confirmed by plain abdominal X-ray and abdominal ultrasound in their health examinations. A blood sample and first spot urine were obtained after getting up for biochemical analysis, including calcium, phosphate, uric acid and creatinine levels. In addition, urinary melamine concentration was measured by the method of triple-quadrupole liquid chromatography tandem mass spectrometry (LC-MS/MS).
Results:
(1) 11 uric acid urolithiasis (median: 0.50 vs 0.06 μg/mmol creatinine, Wilcoxon test: FDR_p = 0.024) and 22 calcium urolithiasis (median: 0.14 vs 0.06, FDR_p = 0.024) had significantly higher urinary melamine concentration than 22 controls.
(2.1) The majority of urolithiasis are calcium urolithiasis (89.4%), therefore, we increase the sample size to examine the relationship of melamine exposure by measuring melamine levels in urine with the risk of calcium urolithiasis. 211 calcium urolithiasis still had significantly higher urinary excretions of melamine than 211 controls (median = 0.21 vs. 0.02 μg/mmol creatinine, p < 0.0001).
(2.2) After adjusting for estimated glomerular filtration rate and other covariates, each one unit (2.718 ?慊/mmol Cr) increase in urinary melamine excretion was associated with a significant 1.84-fold risk (95% CI = 1.48-2.29) of developing calcium urolithiasis (Hosmer-Lemeshow goodness-of-fit test, p = 0.928). Further, then categorized by MDL, > MDL-0.46, and ?d0.47 ?慊/mmole creatinine, a significant trend of increasing calcium urolithiasis risk was also noted [AOR = 2.91 (95%CI: 1.33-6.38); 10.00 (3.90-25.68)] (Hosmer-Lemeshow goodness-of-fit test, p = 0.590).
(2.3) A receiver operating characteristic curve (ROC curve) examining the ability of melamine concentration to discriminate between case patients and controls showed an area under the curve of 0.84 (95%CI = 0.80 to 0.88, p < 0.0001). The optimal cut-off value for urinary melamine excretion was set at 0.024 μg/mmol creatinine with 91.0% sensitivity, 65.4% specificity, 72.5% positive predictive rate and 87.9% negative predictive rate for identifying calcium urolithiasis. When compared with the area under the ROC curve in result (1), the results were not significantly different (p = 0.130).
(2.4) The population attributable risk (PAR%) for calcium urolithiasis ranged 36.6%-68.4% in urinary melamine, after considering urinary uric acid (77.4%-80.3%), fluid intake (51.0%-55.4%), and other covariates. When all 3 factors combined together, to 93.9%-95.7%.
Conclusion: To our knowledge, this is the first one to report the positive association between melamine exposure and the risk of urolithiasis. The etiology of calcium urolithiasis is multifactorial, and some of them are not well-known. Meanwhile, the detailed mechanism about why melamine exposure causes renal stone formation is still unclear. We will focus on more understand the risk and mechanism of formation of renal calcium urolithiasis to benefit how to screen, prevent and treat those urolithiasis patients.
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