Identification of biomarkers for melamine-induced nephrolithiasis in young children based on ultra high performance liquid chromatography coupled to time-of-flight mass spectrometry (U-HPLC–Q-TOF/MS)

Milk products contaminated with melamine caused renal disease in young children in mainland China in 2008. The present study was designed to identify potential markers and assess the underlying metabolomic mechanisms of melamine-induced nephrolithiasis in young children. Urine samples were collected from healthy children (n = 74) and from children diagnosed with nephrolithiasis (n = 73) with either a positive (n = 40) or a negative (n = 33) history of melamine exposure. Ultra high-performance liquid chromatography coupled to time of flight mass spectrometry (U-HPLC–MS/MS) was applied to profile the abundances of metabolites. Partial least squares-discriminant analysis (PLS-DA) was used to discriminate between the samples. Seven compounds were found to highly discriminate between healthy controls and nephrolithiasis patients with a history of melamine exposure. The critical markers such as proline and 5C-aglycone were the predominant markers in the control group and detected only rarely in nephrolithiasis patients with a history of melamine exposure. In contrast, hypoxanthine at was the most significant compound that distinguished nephrolithiasis patients with a history of melamine exposure. It was increased to 116.12 ± 23.34 μg/L (mean ± S.D.) in the melamine-induced nephrolithiasis group, whereas the non-melamine group was at the level of 67.47 ± 9.33 μg/L (p < 0.001). The biomarkers for melamine-induced nephrolithiasis identified by this study may have clinical application in determining the aetiology of renal disease in young children.

► We applied the metabolomics approach to assess the mechanisms of melamine-induced nephrolithiasis in young children.
► Using the nephrolithiasis patients with no history of melamine exposure to filter out biomarkers unique to the melamine-induced nephrolithiasis group.
► Examining hypoxanthine and proline significantly distinguishing the controls/melamine exposure groups.
► The predictive model showed the good performance to identify the markers.