It has been recently suggested that overactive bladder (OAB) may lump together multiple subtypes underpinned by specific pathophysiology. Recognizing those phenotypes may help to tailor the treatment and improve the success rate of first-line and second line OAB therapies. The objective of this study was to evaluate the association between the level of 5 urinary markers (NGF, BDNF, TIMP-2, TGF-B1, and PGE2) and the characteristics of patients with overactive bladder underpinned by detrusor overactivity (OAB-DO) and their possible association with response to treatment

A single-center prospective study was conducted between March 2015 and June 2017 including all consecutive patients with OAB referred for urodynamics in whom filling cystometry evidenced detrusor overactivity. At the end of the inclusion period, the urine samples were unfrozen to assess the level of NGF, BDNF, TIMP-2, PGE2, TGF-B1 using dedicated ELISA kits. The association between urinary marker levels and patient characteristics was investigated using univariate logistic and linear regression

Forty-three patients were included all with non-neurogenic OAB underpinned by detrusor overactivity on urodynamics. There were 18 males and 21 females. The median BMI was 24.6 kg/m2. Five patients had concomitant fecal incontinence (11.9%) and four patients had diabetes mellitus (9.5%). Eleven patients had affective disorders (30.9%). The median volume at first uninhibited detrusor contraction was 182 ml. Patients with affective disorders (anxiety, depression) had significantly higher levels of NGF/Cr (2.04 vs. 0.07 pg/mg creatinine; p=0.006) and significantly lower levels of PGE2/Cr compared to other patients (40.6 vs. 83.4 pg/mg creatinine; p=0.008). There were no other statistically significant associations between urinary markers and patient characteristics. There was also no association between urinary marker levels and response to anticholinergics. In contrast, patients who responded to posterior tibial nerve stimulation (PTNS) had significantly lower BDNF/Cr levels (3.5 vs. 7.6 pg/mg creatinine; p=0.03).

In this study, there was a molecular signature in the subgroup of patients with affective disorders with significantly higher NGF and significantly lower PGE2 levels compared to other OAB-DO patients. This suggests that the pathophysiology of OAB in patients with affective disorders may be specific involving more the neurotrophin pathways and less the inflammatory mechanisms.

These results reinforce the hypothesis of an OAB phenotype associated with anxiety/depression with a specific pathophysiology. BDNF/Cr may be predictive of response to PTNS. Overall, these findings suggest that urinary biomarkers may help to identify pathophysiological mechanisms underpinning OAB and hypothetically help to individualize OAB treatment. Further studies are needed to confirm these findings