**5. Serum biomarkers**

194 Urinary Incontinence

The presence and role of BDNF in the bladder has been scarcely analysed and available results mostly refer to rodent models of bladder dysfunction. Like NGF, BDNF can be synthesized by bladder cells, most notably the urothelium during cystitis (Pinto et al., 2010a) or spinal cord injury (Vizzard, 2000). The expression of TrkB is also abundant in sensory neurons innervating the bladder wall (Qiao & Vizzard, 2002; Murray et al., 2004). Like in somatic tissue (Kerr et al., 1999; Thompson et al., 1999), BDNF expression in the bladder seems to be under the control of NGF (Schnegelsberg et al., 2010; Girard et al., 2011). BDNF appears to be a key participant in bladder dysfunction in an animal model of cystitis as its sequestration improved both bladder reflex activity and peripheral hypersensitivity (Frias et

In humans, it has been reported that urinary BDNF is elevated in patients suffering from bladder pain syndrome/interstitial cystitis (Pinto et al., 2010b). In OAB, a recent study demonstrated that urinary BDNF was also elevated and significantly decreased after therapeutic intervention (Antunes-Lopes et al., 2011). In addition, the concentration of urinary BDNF was shown to be decreased to normal values after successful OAB treatment (Antunes-Lopes et al., unpublished observations). This may indicate that, like NGF (Kuo et al., 2010a), urinary BDNF may serve as an OAB biomarker. However, further studies are necessary to fully understand the importance of BDNF in OAB, particularly how it can

There is a considerable interest in urine as a source of biomarkers for bladder pathologies, OAB assuming one of the foremost active areas of research. Indeed, urine is one of the most versatile biofluids as it can be easily obtained in large quantities with non-invasive methods and is stable in comparison with other fluids. Several peptides and low molecular weight proteins can be found in urine. When urine is collected for analysis, most of them should have undergone physiological proteolysis as urine may stagnate for hours in the bladder before micturition occurs. This might constitute an advantage as, in contrast with blood, serum or plasma, urinary proteins and peptides will not undergo further degradation upon

With the advent and improvement of proteomic analysis, increasing attention has been given to the description of the urinary proteome. The number of proteins identified in the human urine is still increasing and is well above 1500 (Adachi et al., 2006; Good et al., 2010). The combination of different analysis methods and sample treatment recently allowed the identification of more than 100 000 peptides, 5000 of which were present in more than 40% of the individuals analysed (Coon et al., 2008). Several methods are currently being used to analyse the urinary proteome, including two dimensional gel electrophoresis mass spectrometry (2DE-MS), liquid chromatography MS (LC-MS), surface-enhanced laser desorption/ionization (SELDI-TOF) and capillary electrophoresis MS (CE-MS). If interested in more details and the specific advantages and disadvantages of each method, the readers

With the recent advances in urinary proteomics, researchers are becoming more aware of problems arising during storage and preparation of samples. One important issue is the

are advised to seek that information elsewhere (Decramer et al., 2008).

**3.3.2 Brain Derived Neurotrophic Factor (BDNF)** 

al., 2009; Pinto et al., 2010a).

influence the OAB outcome.

**4. Urinary proteomics** 

collection (Kolch et al., 2005; Omenn et al., 2005).

### **5.1 C- reactive protein (CRP)**

CRP is a highly conserved plasma protein. It was identified in the 1930's in the sera of patients in the acute phase of pneumonia by Tillet and co-workers (Tillett & Francis, 1930; Black et al., 2004). Further studies demonstrated that the concentration of CRP in plasma is significantly increased during inflammatory states, a characteristic that has often been used for diagnostic purposes. In what concerns the urinary tract, plasma CRP has been used to monitor the progression of bladder cancer (Hilmy et al., 2006; Gakis et al., 2011a; Gakis et al., 2011b). As far as we are aware, CRP has been addressed in OAB only in a recent pilot study. Chung and co-workers observed higher levels of serum CRP in OAB patients than in controls, particularly in the group of OAB wet patients (Chung et al., 2011). Both urinary CRP and the amount of CRP mRNA present in the bladder wall were very low, indicating that the serum is the body fluid of choice to measure this protein. However, one should be aware that serum CRP would most likely reflect the presence of any inflammatory condition (Black et al., 2004), making its use as a putative biomarker in OAB is very modest.

#### **5.2 Serum NGF**

Like in urine, the presence of NGF in the serum of OAB patients has also been investigated (Liu et al., 2011b). The authors found a positive correlation between urinary and serum NGF contents. Interestingly, serum NGF remained elevated in OAB patients not responding to antimuscarinic treatment, suggesting that increased circulating NGF may be a factor in refractory OAB. This is, however, the only available study regarding serum NGF levels in OAB. It is presently not clear if the high content of NGF in the serum was strictly associated with OAB or dependent on associated comorbidities (hypertension, diabetes, coronary arterial disease, etc.) (Brown et al., 2000). More studies are needed in order to fully understand the relevance of serum NGF in OAB.
