A capillary electrophoresis coupled to mass spectrometry pipeline for long term comparable assessment of the urinary metabolome.

Although capillary electrophoresis coupled to mass spectrometry (CE-MS) has potential application in the field of metabolite profiling, very few studies actually used CE-MS to identify clinically useful body fluid metabolites. Here we present an optimized CE-MS setup and analysis pipeline to reproducibly explore the metabolite content of urine. We show that the use of a beveled tip capillary improves the sensitivity of detection over a flat tip. We also present a novel normalization procedure based on the use of endogenous stable urinary metabolites identified in the combined metabolome of 75 different urine samples from healthy and diseased individuals. This method allows a highly reproducible comparison of the same sample analyzed nearly 130 times over a range of 4 years. To demonstrate the use of this pipeline in clinical research we compared the urinary metabolome of 34 newborns with ureteropelvic junction (UPJ) obstruction and 15 healthy newborns. We identified 32 features with differential urinary abundance. Combination of the 32 compounds in a SVM classifier predicted with 76% sensitivity and 86% specificity UPJ obstruction in a separate validation cohort of 24 individuals. Thus, this study demonstrates the feasibility to use CE-MS as a tool for the identification of clinically relevant urinary metabolites.

Assessment of ureterovesical jet dynamics in obstructed ureter by urinary stone with color Doppler and duplex Doppler examinations.

This study was designed to evaluate ureterovesical jet dynamics in obstructed ureter and to compare it with those of contralateral unobstructed side. Forty-six patients with diagnosis of ureteral stone, based on imaging findings in computed tomography were enrolled in this study. The gray-scale ultrasound exam from both kidneys and urinary bladder was performed. Then, ureterovesical jet characteristics including ureteral jet frequency, duration and peak velocity were assessed by color Doppler and duplex Doppler studies in both obstructed and unobstructed ureters by a radiologist, 15-30 min after oral hydration with 750-1,000 mL of water. When compared with contralateral normal side, the ureterovesical jet in obstructed ureter showed less frequency (0.59 vs. 3.04 jets/min; P < 0.05), shorter duration (1.24 vs. 5.26 s; P < 0.05) and lower peak velocity (5.41 vs. 32.09 cm/s; P < 0.05). The cut-off points of 1.5 jets/min, 2.5 s and 19.5 cm/s for difference of ureteral jet frequency, duration and peak velocity between obstructed and contralateral normal ureters yielded sensitivities of 97.8, 95.6 and 100 % and specificities of 87, 87.9 and 97.8 %, respectively for diagnosis of ureteral obstruction. Given the safety of Doppler study and significant differences in flow dynamics of obstructed versus unobstructed ureters, our findings demonstrated the utility of Doppler ultrasound examination as a useful adjunct to gray-scale ultrasound by improving the accuracy of ultrasound exam in diagnosis of ureteral obstruction.

The value of newborn urinary proteome analysis in the evaluation and management of ureteropelvic junction obstruction: a cost-effectiveness study.

PURPOSE: The cornerstone of management in newborns with ureteropelvic junction obstruction (UPJO) is serial imaging over time. Surgery is undertaken for disease progression. A marker of disease progression would select out those likely to progress for early surgery and diminish the intensity of imaging and follow-up in the remainder. Recently, urinary proteome analysis in the newborn has been reported to fulfill this aim. The objective of this study is to quantitatively evaluate the effect of this matrix of protein biomarkers on the overall cost-effectiveness (C-E) of UPJO evaluation and management. METHODS: A Markov process decision tree model (Tree Age Pro software, Boston, MA) is created to compare the current strategy (watchful waiting) to one incorporating a urine proteome analysis at birth as a marker of disease progression. The analysis includes the costs of surgery, imaging and office visits based on hospital charge data. We analyze a total of 53 variables. RESULTS: The incorporation of this marker of progression results on the average, in an incremental C-E gain of 8,000 US dollars per quality adjusted life year (QALY) per patient compared to the current strategy of watchful waiting. The results are not sensitive to variation of any of the probabilities including costs and quality of life parameters used for the base-case analysis. CONCLUSIONS: The incorporation of urinary proteome analysis in the initial evaluation of UPJO significantly reduces costs and increases the QALYs in this patient population. The test increases the odds of detecting UPJO progression from 1:3 to 1:1, while improving the overall C-E. These findings justify continued research in this area which in addition may have important applications in evaluating treatment outcomes.