New participant stratification and combination of urinary biomarkers and confounders could improve diagnostic accuracy for overactive bladder.

Overactive bladder (OAB) is a highly prevalent symptom complex characterised by symptoms of urinary urgency, increased frequency, nocturia, with or without urge incontinence; in the absence of proven infection or other obvious pathology. The underlying pathophysiology of idiopathic OAB is not clearly known and the existence of several phenotypes has been proposed. Current diagnostic approaches are based on discordant measures, suffer from subjectivity and are incapable of detecting the proposed OAB phenotypes. In this study, cluster analysis was used as an objective approach for phenotyping participants based on their OAB characteristic symptoms and led to the identification of a low OAB symptomatic score group (cluster 1) and a high OAB symptomatic score group (cluster 2). Furthermore, the ability of several potential OAB urinary biomarkers including ATP, ACh, nitrite, MCP-1 and IL-5 and participants' confounders, age and gender, in predicting the identified high OAB symptomatic score group was assessed. A combination of urinary ATP and IL-5 plus age and gender was shown to have clinically acceptable and improved diagnostic accuracy compared to urodynamically-observed detrusor overactivity. Therefore, this study provides the foundation for the development of novel non-invasive diagnostic tools for OAB phenotypes that may lead to personalised treatment.

Correlation of urine and plasma cytokine levels among reproductive-aged women.

BACKGROUND: Inflammation is implicated in many adverse health conditions, and recent interest has focused on the effects of chronic low-grade inflammation in generally healthy populations. Cytokines measured in plasma or serum are commonly used as biomarkers of systemic levels of inflammation. Measurement of cytokines in urine may offer a simpler and less invasive alternative, although the degree to which levels of cytokines correlate in plasma and urine among healthy individuals is unknown. MATERIALS AND METHODS: We assessed the correlation of blood and urine levels of 13 cytokines, including interleukin (IL)-1b, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12(p70) and IL-13, granulocyte macrophage colony-stimulating factor, interferon gamma and tumour necrosis factor alpha in 61 healthy women aged 18-30. Cytokine concentrations were considered with and without correction for creatinine. RESULTS: Plasma and urine levels of the 13 cytokines were not significantly correlated using measured urinary cytokine concentrations and after adjustment for creatinine. Correlation coefficients for log-transformed cytokine concentrations in paired plasma and urine specimens ranged from -0.28 to 0.087. CONCLUSIONS: These results suggest that urine has limited utility as a proxy for plasma for the measurement of inflammatory factors in a healthy population with low levels of inflammation.

Inflammatory mediators release in urine from mice injected with Crotalus durissus terrificus venom.

In this study, we investigated in groups of female BALB/c mice injected with Crotalus durissus terrificus venom (Cdt) the renal function based on creatinine clearance, percentage of fractional excretion cytokines and histological examination of renal tissue. Cdt caused renal alterations that induced proteinuria during the initial hours post-venom and reduced creatinine clearance 15 min. up to 2 hours post-venom administration. In urine from mice injected with Cdt induced a decrease in IL-4 levels. More pronounced increments of IL-5, IL-6 and IFN-γ were observed after 15 and 30 min, respectively. The highest levels of TNF and IL-10 were observed at 1 and 4 hs, respectively. The ratios of pro- and anti-inflammatory cytokines in animals injected with Cdt, which may be manifested in the inflammatory status during the envenoming. In groups of animals treated with Cdt were observed a decreasing in creatinine clearance and its effect on glomerular filtration rate was accompanied by decreased fractional excretion of cytokines and morphologic disturbances. This loss of change selectively in envenomation could thus explain why the relatively excretion of cytokines is reduced while of total proteins increases. In conclusion the fractional excretion of cytokines is significantly reduced in mice injected with Cdt, despite proteinuria.

Urine cytokines suggest an inflammatory response in the overactive bladder: a pilot study.

PURPOSE: To study the hypothesis of detecting bladder inflammation associated with overactive bladder (OAB) through altered urine levels of cytokines, chemokines, and growth factors. METHODS: Midstream urine specimens were collected from a prospective study done on eight asymptomatic control subjects and 17 idiopathic OAB patients. The urine was analyzed by a multiplex panel screen for 12 chemokines, cytokines, growth factors, and soluble receptors using Luminex™ xMAP(®) technology. Protein concentration values were normalized to the levels of creatinine. RESULTS: This analysis revealed a significant elevation of seven key proteins in the urine of OAB patients relative to controls (*P < 0.05). A greater than tenfold elevation was measured in OAB, relative to controls, in the levels of monocyte chemotactic protein-1 (MCP-1), soluble fraction of the CD40 ligand (sCD40L) in urine was obtained from OAB patients relative to controls. At least five fold elevations were detected in the levels of macrophage inflammatory protein (MIP-1ß), IL-12p70/p40, IL-5, epidermal growth factor (EGF), and growth-related oncogene GRO-α compared to controls. Significant threefold elevation was also noticed in the urine levels of sIL-2Rα, and IL-10 in the OAB group. The levels of the remaining proteins tested were not statistically significantly different from control values. CONCLUSIONS: The presence of elevated levels in urine of inflammatory biomarkers involved in inflammation and tissue repair suggests a role for inflammation in OAB, and may help in diagnosis and treatment of this disease.