Increased oxidative stress in the detrusor of men with bladder outlet obstruction

Averbeck M A1, De Lima N G2, Motta G A3, Beltrao L3, Abboud Filho N J3, Rigotti C P3, Dos Santos W N3, Dos Santos S K J3, da Silva L F B3, Rhoden E L4

Research Type

Basic Science / Translational

Abstract Category

Male Lower Urinary Tract Symptoms (LUTS) / Voiding Dysfunction

Abstract 305
Bladder Outlet Obstruction
Scientific Podium Short Oral Session 18
Thursday 30th August 2018
12:57 - 13:05
Hall A
Bladder Outlet Obstruction Male Pathophysiology
1. Moinhos de Vento Hospital, Porto Alegre, Brazil & Federal University of Health Sciences of Porto Alegre (UFCSPA), 2. Hospital Nossa Senhora dos Navegantes, Torres, Brazil, 3. Federal University of Health Sciences of Porto Alegre (UFSCPA), 4. Moinhos de Vento Hospital, Santa Casa Hospital Complex & Federal University of Health Sciences of Porto Alegre (UFSCPA)
Presenter
M

Marcio Augusto Averbeck

Links

Abstract

Hypothesis / aims of study
This study aimed to evaluate the link between preoperative parameters and oxidative stress (OS) markers in the bladder wall of men undergoing open prostate surgery. We hypothesized that severe bladder outlet obstruction (BOO) was associated with increased OS in the detrusor of men with lower urinary tract symptoms (LUTS).
Study design, materials and methods
From July 2014 to August 2016, men aged ≥ 50 years and presenting with LUTS were prospectively enrolled. We collected clinical, and anthropometric data such as age, comorbidities, weight, height, body mass index (BMI), fasting glucose, and blood pressure. Preoperative assessment also included validated questionnaires (IPSS and OAB-V8), lower urinary tract ultrasound and urodynamics. Urodynamic studies were performed 2 to 3 weeks before open prostatectomy, using the Laborie Dorado KT® device (Laborie Medical, Ontario, Canada). All assessments were performed by a single trained researcher, in compliance with the International Continence Society (ICS) Good Urodynamic Practices.  Bladder biopsies were taken during open prostatectomy for determination of OS markers. Our primary endpoint was the association between OS markers and severity of BOO. Exploratory endpoints included the link between OS markers various preoperative characteristics, such as obesity, severity of LUTS, overactive bladder symptoms, ultrasound and urodynamic parameters. Increased OS was defined by increased concentration of malondialdehyde (MDA) and/or decreased concentration of antioxidant enzymes (superoxide dismutase and/or catalase). OS and preoperative parameters were compared using the Student T test. P<0.05 was regarded as statistically significant.
Results
Thirty-eight consecutive patients were included. Mean age was 66.36 ± 6.44 years. Mean body mass index (BMI) was 26.36 ± 2.98 kg/m2. The most common comorbidities were systemic arterial hypertension (50%) and diabetes mellitus type 2 (DM2) (29%). Regarding LUTS severity, 14 patients (36.8%) presented mild symptoms, 18 (47.3%) moderate and 6 (15.7%) severe symptoms. Prevalence of overactive bladder symptoms (OAB-V8 score ≥ 8 points) was 36.8% (n=14).  Mean prostate volume estimated by transabdominal ultrasound was 77.7 ± 20.63 cm3. Mean bladder wall thickness (BWT) was 3.99 ± 1.39 mm. 
Primary endpoint: BOO was observed in 29 patients (76.3%). MDA concentration was increased in men with severe BOO (zone V or VI on Schaefer’s nomogram; figure 1) (p=0.022). 
Exploratory endpoints: Patients with severe LUTS (IPSS score ≥ 20 points) had higher MDA concentration in the bladder wall when compared to the patients with mild LUTS (IPSS <8 points): 290.93 ± 237.87 vs. 111.93 ± 82.37 pmol/mg, respectively (p=0.031). Otherwise, the diagnosis of OAB (OAB-V8 score ≥8 points) had no association with increased OS in the bladder wall (p > 0.05). There was a statistically significant association between increased post-void residual urine (cutoff ≥ 50 ml) and OS in the bladder (higher levels of MDA and reduced activity of both antioxidant enzymes) (p<0.05). 
Obesity was associated with reduced activity of the antioxidant enzyme catalase (170.88 ± 27.46 vs. 317.11 ± 268.98 pmol/mg in obese and in non-obese patients, respectively; p=0.01) and with reduced activity of the antioxidant enzyme SOD (0.4 ± 0.19 vs. 0.76 ± 0.59 Usod/mg in obese and in non-obese patients, respectively; p=0.05). MDA concentration was higher in patients with BWT ≥ 3 mm compared to those with BWT < 3 mm (342.03 ± 317.03 vs. 157.97 ± 107.47 pmol/mg, respectively; p=0.015).
Interpretation of results
To our knowledge, this is the first study investigating OS markers (MDA, SOD and catalase) in the detrusor muscle of humans undergoing open prostate surgery. Clinical factors (LUTS severity and obesity, ultrasound findings (bladder wall thickness ≥ 3 mm), and urodynamic parameters (BOO severity, post-void residual urine ≥ 50 ml) were associated with increased OS in the detrusor. Identification of such factors may have clinical relevance, as evidence from animal models suggested a relationship between increased OS and bladder dysfunction (1-3).
Concluding message
This pilot study showed that increased OS in the detrusor of men with LUTS was associated with severe BOO and other preoperative parameters. Further studies are still needed to assess the role of non-invasive biomarkers of OS in predicting bladder dysfunction in men with LUTS.
Figure 1
References
  1. Azadzoi KM, Yalla SV, Siroky MB. Human bladder smooth muscle cell damage in disturbed oxygen tension. Urology. 2011;78(4):967.e9-15.
  2. Callaghan CM, Schuler C, Leggett RE, Levin RM. Effect of severity and duration of bladder outlet obstruction on catalase and superoxide dismutase activity. Int J Urol. 2013;20(11):1130-5.
  3. Malone L, Schuler C, Leggett RE, Levin RM. The effect of in vitro oxidative stress on the female rabbit bladder contractile response and antioxidant levels. ISRN Urol. 2013;2013:639685.
Disclosures
<span class="text-strong">Funding</span> None <span class="text-strong">Clinical Trial</span> No <span class="text-strong">Subjects</span> Human <span class="text-strong">Ethics Committee</span> 660.810 <span class="text-strong">Helsinki</span> Yes <span class="text-strong">Informed Consent</span> Yes