## 3 Metabolic Profiling of Urine: Recent Trends
For example, after soya consumption, daidzein, genistein and total isoflavoids were found to be higher in urine samples [44], but in turn, the same urinary levels of genistein, total isoflav and metabolites were reduced during antibiotic use [39]. For the development of specific biomarkers, it is important to decipher the complex molecular networks that characterize disease states [38]. For instance, the diagnostics methods that are usually employed are incapable of predicting jaundice syndrome (JS) in patients with liver disease. However, the results of one metabolomic study clearly revealed the potential of urine metabolomics in the diagnosis of this pathophysiology [45]. Urinary metabolites may be also very important for the non-invasive screening of pre-diabetic subtypes, which could lead to an early and personalized intervention for this disease [38]. Aiming for the characterization of metabolic indicators for type 2 diabetes mellitus (T2 DM), [PERSON] _et al._[46] used LC-MS, GC-MS and NMR data from urinalysis to report a cross-platform for the urinary metabolome of T2 DM. This allowed them to show significant up and down variations in the levels of several metabolites under hyperglycemia in T2 DM. Uranalysis has been also used to search for metabolite signatures that could be associated with cancer. In this way, several studies showed that low molecular weight urinary volatile organic compounds (VOCs) could be used as biomarkers for lung cancer, urine metabolomics having an excellent sensitivity (93%) and specificity (94%). Some metabolites of interest included \(\beta\)-hydroxyisovalerate, hyppurate, \(\alpha\)-hydroxyisobutyrate and creatinine [38, 47]. Regarding the high prevalency breast and ovarian cancers, some qualitative and quantitative metabolomic methodologies have shown promising metabolic changes. [PERSON] _et al._[48], for instance, using NMR urinalysis, reported that intermediates of the tricarboxylic acid cycle and metabolites related with energy metabolism, amino acids and gut microbial metabolism were perturbed. This data is in agreement with the report from [PERSON] _et al._[49], showing that several metabolic biomarkers related to glycolysis, mitochondrial citric acid cycle, choline and fatty acid metabolism are important in carcinogenesis and are responsive to anticancer treatment. Regarding this, [PERSON] _et al._[50] performed a targeted metabolite profiling of 14 urinary nucleosides in pre- and post-operative breast cancer female patients. The results showed levels of modified nucleosides (5-hydroxymethyl-2'-deoxyuridine, 8-hydroxy-2' -deoxyguanosine (8-OHdG), 1-methyladenosine and N(2),N(2)-dimethylguanosine) as being significantly higher in pre-operative patients than in both normal controls and post-operative patients. In the same direction, [PERSON] _et al._[51] observed a positive association between the urinary level of the oxidative stress biomarker, 8-OHdG, and the risk of especially estrogen receptor-positive breast cancers. Finally, [PERSON] _et al._[52] reported that urinary levels of homovanillate, 4-hydroxyphenylacetate, 5-hydroxyindoleacetate and urea were also altered in breast cancer patients. Acute kidney injury (AKI) is another extensively studied clinical perturbation, due to its high incidence, mortality and morbidity. This justifies the search for suitable biomarkers, as the existing one, the monitoring of serum creatinine, presents poor analytical performance, being unspecific for AKI and highly influenced by other variables, such as gender, age, muscle mass and metabolism, drugs and hydration. Furthermore serum creatinine is not targeted for the early detection of disease [37]. Therefore, urine became a preferred matrix to search for new biomarkers for renal injury. Regarding this, [PERSON] _et al._[53] studied the potential of urine metabolomics to find important metabolites in kidney cancer and reported that some compounds related with amino acid and energy metabolism, such as quinolate, 4-hydroxybenzoate and gentisate, were differentially expressed [38].