NMR-based metabonomic analysis is a well-established approach to characterizing healthy and diseased states. The aim of this study was to investigate inter-individual variability in the metabolic urinary profile of a healthy Greek population, not subjected to strict dietary limitations, by NMR-based metabonomics. The overall metabonomic urinalysis showed a homogeneous distribution among the population. The metabolic profile was examined in relation to gender and age, and reference intervals of major metabolites were determined. Multivariate data analysis led to the construction of two robust models that were able to predict the class membership of the subjects studied according to their gender and age. The most influential low molecular weight metabolites responsible for the differences in gender groups were citrate, creatinine, trimethylamine N-oxide, glycine, creatine and taurine, and for the differences in age groups they were citrate, creatinine, trimethylamine N-oxide and an unidentified metabolite (d 3.78).

An 1H NMR-based metabonomic approach was used to investigate the correlation of histopathologically assessed tubulointerstitial lesions with the urinary metabolite profile in 77 patients with glomerulonephritides submitted to renal biopsy. The presence of renal damage was predicted with a sensitivity of 96% and a specificity of 99%. Patients with mild, moderate, and severe tubulointerstitial lesions were progressively differentiated from the healthy individuals in the Orthogonal Signal Correction Partial Least-Squares-Discriminant Analysis (OSC/PLS-DA) models with a statistically significant separation between those with mild and with severe lesions. The onset of the tubulointerstitial lesions is characterized by decreased excretion of citrate, hippurate, glycine, and creatinine, whereas further deterioration is followed by glycosuria, selective aminoaciduria, total depletion of citrate and hippurate, and gradual increase in the excretion of lactate, acetate, and trimethylamine-N-oxide. NMR-based metabonomic urinalysis could contribute to the early evaluation of the severity of the renal damage and possibly to the monitoring of kidney function.

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