Bowel Habits and the Association With Uremic Toxins in Non-Dialysis-Dependent Chronic Kidney Disease Patients.

OBJECTIVE: The aim of this study is to evaluate the association between bowel habits and microbial-derived uremic toxins p-cresyl sulfate (PCS) and indoxyl sulfate (IS) in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD). DESIGN AND METHODS: This is a cross-sectional analysis including 43 nondiabetic NDD-CKD patients (58% men; 59.0 ± 13.5 years; estimated glomerular filtration rate, 21.3 ± 7.9 mL/min/1.73 m2). Bowel habit was assessed by the Bristol Stool Scale (BSS <3, characterized by hard consistency of stools and/or low frequency of evacuation and BSS ≥3, representing a more regular bowel habit) and by the Rome III criteria. PCS and IS (serum, free and total; urinary, total) were determined by high-performance liquid chromatography. Dietary intake was assessed by the 3-day food records. RESULTS: The frequency of constipation assessed by BSS and Rome III criteria was 33% (n = 14/43) and 35% (n = 15/43), respectively. The BSS <3 exhibited higher PCS, independent of renal function and dietary protein-fiber ratio (ß [95% confidence interval {CI}]: serum, total PCS = 1.54 [1.06-2.23], P = .02; serum free PCS = 1.40 [1.00-1.97], P = .05; urinary PCS = 1.78 [1.10-2.90], P < .02). According to the Rome III criteria, a tendency for a higher serum total PCS (ß [95% CI]: 1.39 [0.95-2.03 µmol/L], P = .09) and a significantly higher urinary PCS (ß [95% CI]: 1.80 [1.11-2.94 µmol/24 h], P = .02) was found in constipated participants. No effect of a compromised bowel habit (Rome III criteria or BSS) was found on IS. CONCLUSION: Constipation may lead to production of PCS in nondiabetic NDD-CKD patients.

Spot urinary 5-hydroxyindoleacetic acid is not an ideal diagnostic test for acute appendicitis.

BACKGROUND AND PURPOSE OF THE STUDY: There is growing evidence to suggest the use of urinary 5-hydroxyindoleacetic acid (5-HIAA) test to help with the diagnosis of appendicitis. The aim of our study was to establish whether urinary 5-HIAA could be used as an effective diagnostic test for acute appendicitis. DESIGN AND METHODS: A prospective double-blinded study was carried out from December 2014 to October 2015. Patients admitted to the emergency surgical ward of a teaching hospital with suspected appendicitis were included in the study. The diagnostic accuracy of the test was measured by receiver operating characteristic curve. RESULTS: Ninety-seven patients were divided into 2 groups: acute appendicitis (n=38) and other diagnosis (n=59). The median value of urinary 5-HIAA was 24.19µmol/L (range, 5.39-138.27) for acute appendicitis vs 18.87µmol/L (range, 2.27-120.59) for other diagnosis group (P=.038). The sensitivity and specificity of urinary 5-HIAA at a cutoff value of 19µmol/L were 71% and 50%, respectively. Receiver operating characteristic analysis showed that the area under curve was 0.64 (confidence interval [CI], 0.513-0.737) for urinary 5-HIAA, which was lower than white blood cell count (0.69; CI, 0.574-0.797), neutrophil count (0.68; CI, 0.565-0.792), and C-reactive protein (0.76; CI, 0.657-0.857). There was no significant difference in the median values of 5-HIAA between different grades of severity of appendicitis (P=.704). CONCLUSION: Urinary 5-HIAA is not an ideal test for the diagnosis of acute appendicitis.

Urinary proteome analysis of irritable bowel syndrome (IBS) symptom subgroups.

Irritable bowel syndrome (IBS) is a functional gastrointestinal (GI) disorder characterized by chronic abdominal pain associated with alterations in bowel function. Given the heterogeneity of the symptoms, multiple pathophysiologic factors are suspected to play a role. We classified women with IBS into four subgroups based on distinct symptom profiles. In-depth shotgun proteomic analysis was carried out to profile the urinary proteomes to identify possible proteins associated with these subgroups. First void urine samples with urine creatinine level≥100 mg/dL were used after excluding samples that tested positive for blood. Urine from 10 subjects representing each symptom subgroup was pooled for proteomic analysis. The urine proteome was analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using a data-independent method known as Precursor Acquisition Independent From Ion Count (PAcIFIC) that allowed extended detectable dynamic range. Differences in protein quantities were determined by peptide spectral counting followed by validation of select proteins with ELISA or a targeted single reaction monitoring (LC-SRM/MS) approach. Four IBS symptom subgroups were selected: (1) Constipation, (2) Diarrhea+Low Pain, (3) Diarrhea+High Pain, and (4) High Pain+High Psychological Distress. A fifth group consisted of Healthy Control subjects. From comparisons of quantitative spectral counting data among the symptom subgroups and controls, a total of 18 proteins that showed quantitative differences in relative abundance and possible physiological relevance to IBS were selected for further investigation. Three of the 18 proteins were chosen for validation by either ELISA or SRM. An elevated expression of gelsolin (GSN) was associated with the high pain groups. Trefoil Factor 3 (TFF3) levels were higher in IBS groups compared to controls. In this study, the IBS patients subclassified by predominant symptoms showed differences in urine proteome levels. Proteins showing distinctive changes are involved in homeostasis of intestinal function and inflammatory response. These findings warrant future studies with larger, independent cohorts to enable more extensive assessment and validation of urinary protein markers as a diagnostic tool in adults with IBS.

Purple urine bag syndrome: a community-based study and literature review.

AIM: Purple urine bag syndrome (PUBS) is considered as an uncommon phenomenon. This cohort study aimed to figure out the causative factors and the potential risks of PUBS. METHODS: We recruited 84 patients with long-term urinary catheterization from seven nursing institutions and home care centre, then compared the differences of demographic, clinical, urine test and bacteriological data between the patients with and without PUBS. RESULTS: The 2-month period prevalence of PUBS in chronic catheterized patients was 16.7%. PUBS-affecting patients had significantly higher proportion of female gender (P = 0.034), self oral intake (P = 0.036) and eating self-prepared food (P = 0.007). Otherwise, no statistical associations were found. Five different bacterial species were isolated from the urine of PUBS-affecting patients. No sequelae were found after forward follow-up for 6 months. We further discuss the associations between certain factors and PUBS according to literature review and the results of our study. CONCLUSION: PUBS is not as rare as we thought before. The causative factors of PUBS have not been clearly characterized. It may be the combination of several factors that cause the PUBS. Female gender and food content were found to be associated factors of PUBS in our study. Asymptomatic PUBS is unnecessary to be treated by antibiotics.

A liquid chromatography/mass spectrometry method for the evaluation of intestinal permeability.

OBJECTIVES: Lactulose to mannitol ratio (L/M) in urine is used as a non invasive assay to measure intestinal permeability. We describe here a rapid, specific and sensitive LC-MS/MS method for the measurement of these compounds in urine of children affected by abdominal recurrent pain (ARP). DESIGN AND METHODS: The study has been performed on 50 children from the Pediatric Unit. The chromatographic separation was accomplished by using an NH(2)-column, the detection with a Q-Trap 2000 system. RESULTS: Multiple calibration curve exhibited consistent linearity and reproducibility. Linear responses were observed in the concentration range 0-400 microg/mL for both mannitol and lactulose. Limits of detection were 12.5 mg/L for lactulose and 1.25 mg/L for mannitol with a signal-to-noise ratio of 10. CONCLUSIONS: The comparison of L/M values of healthy children with those found in children affected by idiopathic ARP demonstrates that in the latter subjects an alteration of intestinal permeability occurs. The method can represent a useful tool to monitor the intestinal functionality in children with ARP conditions and help for an accurate patient discrimination for diet restrictions.

Nuevas tendencias en el manejo de la vejiga hiperactiva en pacientes pediátricos / New trends in the management of overactive bladder in pediatric patients

La investigación es una herramienta indispensable para la evolución de los conceptos en cualquier ciencia; la medicina es dinámica, está destinada al cambio y al progreso. Desde hace varios años el tratamiento de los pacientes con desórdenes como la hiperactividad vesical, ha tenido su blanco en el manejo sintomático, dejando aislado el conocimiento de la fisiopatología de esta condición. Grupos como el Departamento de Urología del Colegio Médico de Nueva York, han querido dar un giro al enfoque de esta patología, investigando para entender mejor sus bases1 y poder ofrecer opciones de tratamiento mucho más certeras. La adopción de un enfoque corticocéntrico en el entendimiento de esta enfermedad, parece ser la respuesta a muchos de los interrogantes que surgen al revisar las series de respuesta al manejo médico actual de la hiperactividad vesical.

[Serum serotonin concentration and urine 5-hydroxyindole acetic acid excretion in patients with irritable bowel syndrome]. / Steizenie serotoniny w surowicy krwi i wydalanie kwasu 5-hydroksyindolooctowego z moczem u osób z zespolem jelita nadwraziliwego.

UNLABELLED: Serotonin (5-HT) is among other factors involved in gastrointestinal motility, secretion and visceral sensation. Available data suggest that secretion and metabolism of 5-HT may be disturbed in irritable bowel syndrome (IBS). Interpretation of these observations have been hampered by the variable methodology used and small numbers of patients involved in the previous studies. Aim of this study was to measure serum 5-TH concentration under fasting condition in patients with irritable bowel syndrome (IBS), compared with controls (K). The metabolite of serotonine--5-hydroxyindole acetic acid (5-HIAA) in urine was also assessed. METHODS: 71 subjects, aged 19-50 years were included in this study. Three groups were distinguished: group I (n=25)--healthy volunteers, group II (n=23)--patients with constipation predominant (IBS-C), group Ill (n=23)--subjects with diarrhea predominant irritable bowel syndrome (IBS-D). IBS was diagnosed according to Rome Ill Criteria. On the day of the experiment, patients received a standard meal (Nutridrink 6 x 300 kcal) and blood samples were collected during fasting. 5-HIAA concentration was determined in 24-hour urine collection. Concentration of 5-HT and 5-HIAA was measured by immunoenzyme ELISA method employing standard kits IBL nr RE59121 i RE59131 and Labsystems Multiscan detector. RESULTS: The average serotonin concentration during fasting was found in group I--156.67 +/- 49.12 ng/ml, in group II--221.73 +/- 91.56 ng/ml (p < 0.05), in group III--3.50 +/- 1.71 mg/24h. 5- HIAA concentration in urine was decreased in group Ill--3.50 +/- 1.71 mg/24 hrs (p < 0.05) and group II--4.37 +/- 2.95 mg/24 hrs compared with healthy volunteers--5.65 +/- 2.31 mg/24 hrs. CONCLUSION: (1) Serotonin concentration is increased in C-IBS and D-IBS patients. (2) Urine 5-hydroxyindole acetic acid excretion is decreased in IBS-subjects. (3) Disturbed metabolism of serotonin probably may play role in pathogenesis of functional bowel diseases.

The urinary 5-hydroxyindole acetic acid and plasma nitric oxide levels in irritable bowel syndrome: a preliminary study.

BACKGROUND AND AIMS: Postprandial increase of 5-hydroxytryptamine (5-HT) has been implicated in irritable bowel syndrome (IBS). There is evidence that nitric oxide (NO) may act as a mediator of 5-HT-evoked secretions in the colon. Our aim is to investigate the role of urinary 5-hydroxyindole acetic acid (5-HIAA) and plasma NO levels (with diarrhoea) in IBS patients. METHODS: Nineteen (with constipation) IBS patients (group 1), 22 IBS patients (group 2) and 18 healthy controls (group 3) were included in the study. The diagnosis of IBS was made according to the Rome I Criteria. The urine was collected for determination of 5-HIAA and venous blood was collected from each subject for the measurement of plasma NO levels. RESULTS: The levels of urinary 5-HIAA mmol/day and plasma NO mmol/l of group 1 (22.4 +/- 2.2 and 29.4 +/- 2 respectively) were significantly higher than group 3 (14.2 +/- 2.3 and 21.3 +/- 2.1 respectively) (p = 0.036 and p = 0.019 respectively). The NO level of group 1 was also significantly higher than group 2 (21.8 +/- 1.9) (p = 0.021). The 5-HIAA level of group 1 was higher than group 2 (15.2 +/- 2.1) and the difference was marginally significant (p = 0.055). There was no difference between group 2 and group 3 with respect to 5-HIAA and NO levels. CONCLUSIONS: The results of this preliminary study lend support to the involvement of 5-HT in some symptomatology of diarrhoea predominant IBS. Furthermore, NO may be one of the effector mediators of the 5-HT-induced symptoms in these patients.