Veränderungen von NGF und PGE2 bei Patienten mit überaktiver Blase nach BoNT-A Therapie -Biomarker bei OAB?

This prospectively designed study aims to analyze neurotransmitters nerve growth factor (NGF) and prostaglandin E2 (PGE2) serum blood levels in patients with overactive bladder (OAB) before and after botulinum toxin A (BoNT-A) therapy. Cause and development of OAB are still not fully understood. Currently, chronic inflammatory processes are discussed as a trigger. Different transmitters play an important role both during physiological micturition and bladder disorders. However the exact regulations during micturition are still obscure. Recent studies showed significantly increased urinary NGF and PGE2 levels in OAB patients. Moreover, a significant change in protein levels before and after anticholinergic therapy and BoNT-A treatment could be shown in several studies. Up to now relevant data about serum levels is lacking. We measured serum blood levels of both proteins in patients with OAB before and after BoNT-A therapy. 32 healthy patients served as control group. Evaluation included patient history, urine analysis, a voiding diary and urodynamic studies. Inclusion criteria were urodynamic proven non-neurogenic overactive bladder with detrusor hyperactivity or hypersensitive low capacity bladder without detrusor hyperactivity. Patients were excluded if they did not meet the criteria. All patients were non-responder to medical treatment. Before and 4 weeks after treatment therapeutic success was assessed on the basis of standardized questionnaires ICIQ-SF and KHQ. Before and 4 weeks after BoNT-A treatment, blood samples were collected. Serum blood levels were measured by a commercialized enzyme linked immunosorbent assay. The statistical data analysis was performed using the non-parametric Mann–Whitney U test and paired t-test to compare the different groups and the individual changes. Serum blood levels of the two protein groups differed significantly from controls. Significantly higher sNGF levels were detected in 26 patients with OAB (sNGF 58,8 pg/ml, p<0,005), hereof 18 with OAB wet. Furthermore sNGF levels were increased in patients with OAB wet compared to OAB dry (85 pg/ml (± 250) vs. 0,73 pg/ml (± 2,1). sNGF levels decreased significantly after BoNT-A treatment (2,4 pg/ml, p<0,005). Incontinence pads were needed significantly less frequent . Patients >60 years showed significantly higher sNGF levels (77,2 pg/ml vs. 8,9 pg/ml, p<0.05) compared to younger OAB patients. 2 patients had no significant effect after BoNT-A treatment. They showed no or only slightly decreased sNGF-levels. We could demonstrate equivalent results for sPGE2: significantly higher sPGE2 levels were detected in 56 patients with OAB compared to controls (2750 pg/ml vs. 1674 pg/ml, p<0.005). Furthermore sPGE2 levels were increased in patients with OAB wet compared to OAB dry (3241 pg/ml versus 1734 pg/ml, p<0,01). In 30 patients (53,6%) sPGE2 levels decreased significantly 4 weeks after BoNT-A treatment compared to baseline (2995 pg/ml vs. 1486 pg/ml, p<0.005). Patients reported an average drug effect of 9 month; incontinence pads were needed significantly less frequent (p< 0.05). 3 patients reported no postoperative effect. sPGE2 increased in two patients (66,6%) compared to initial levels (51%), a single patient showed a remotely decreased sPGE2 (-27%). Six patients were treated repeatedly with BoNT-A after showing an sPGE2 re-rise. 4 weeks after BoNT-A treatment sPGE2 levels decreased again. sPGE2 did not correlate with age. Our results clearly demonstrate the relationship between sNGF, sPGE2 and OAB reflected in significantly elevated serum levels of both proteins in patients suffering from OAB. For the first time we present data that sNGF and sPGE2 development is influenced by intravesical BoNT-A therapy in OAB. Moreover, our data detect a correlation of both protein blood levels with the severity of OAB reflected by significant higher levels in wet compared to dry OAB. Furthermore, we detected a correlation between the success of therapy as well as the degree and duration of decreased protein levels. A limitation of this prospective single-center examination was the relatively small patient cohort of 82 OAB-patients. These promising results have to be confirmed in further investigations with a larger population. This possible potential to differentiate between various OAB stages reveals sNGF and PGE2 as promising for future use as markers and additional helpful tools for therapeutic decisions in OAB.