Role of urine glycosaminoglycan levels in the diagnosis and follow-up in men with lower urinary tract symptoms.

OBJECTIVE: The aim of this study was to investigate whether urinary glycosaminoglycans (GAG) levels reflect clinical status in men with lower urinary tract symptoms and if they could be used as a marker in management of overactive bladder (OAB). METHODS: A total of 34 patients were recruited who were admitted with LUTS and diagnosed as having clinically bladder outlet obstruction (BOO) due to prostate enlargement. These newly diagnosed, never treated patients underwent routine investigation, consisting of history, physical examination, PSA, ultrasound, uroflowmetry, assessment of symptoms scored by both International Prostate Symptom Score (IPSS) and Marmara- Overactive Bladder Questionnaire (M-OBQ). The patients were divided into two groups as those with an initial M-OBQ score < 12 (group 1) and ≥ 13 (group 2). Alfa blocker was initiated in eligible patients. Further evaluations included prostate volume measurement, pre- and post-treatment urinary GAG levels, IPSS and M-QAOB values and maximum urine flow rate (Qmax). RESULTS: Before treatment, urinary GAG level was 21.5 mg/gCr (6.1-45.5) in Group 1, and 23.35 mg/gCr (15.6-32.6) in Group 2 (p =0.845). After the treatment, the GAG level in Group 1 and Group 2 were found to be 19.8 mg/gCr (7.4-70.5) and 18 (7.6- 41.7), respectively (p = 0.511). No difference in GAG levels was found in subgroup analysis for patients with or without OAB. CONCLUSIONS: In recent years, there have been many studies investigating the relationship between LUTS and urinary markers. However, in our prospective study, no relationship was found between pre- and post- treatment urinary GAG levels in patients with LUTS with or without OAB.

Mejora de las variaciones en la ecografía vesical Evaluación del volumen de orina residual posmiccional en obstrucción moderada de la salida de la vejiga / Improving Variations in Bladder Ultrasound Assessment of Post-Void Residual Urine Volume in Moderate Bladder Outlet Obstruction

Objectives: This study aimed to assess the accuracy of post-void residual (PVR) urine volume measurements in patients with moderate bladder outlet obstruction. Materials and Methods: This prospective observational study was conducted between January and December 2019. The inclusion criteria were male patients with symptoms of moderate bladder outlet obstruction. On the other hand, patients with a history of diabetes, symptoms of urinary tract infection, and positive urine for pyuria, as well as patients using medications, such as diuretics, alphablockers, and anticholinergic drugs, were excluded. The patients were asked to drink 1000 mL of water one to two hours before the initial ultrasound scan. Pre-void bladder capacity was measured, followed by a post-void ultrasound for residual urine volume measurement at three intervals: immediately after voiding, 15-20 minutes after the first void, and one week later with an empty bladder. Assessment of per-void capacity was carried out, based on the patient's subjective sensation of bladder fullness (a strong desire to void). Results: A total of 78 male patients, with the mean age of 60 years, were included in this study (27 cases in group I; 37 cases in group II; and 14 cases in group III). The mean PVR volume was 92 mL in the first measurement, 62 mL in the second measurement, and 60 mL in the third measurement. Significant differences were found between the first and second PVR measurements and between the first and third PVR measurements (P<0.05). However, no significant difference was found between the second and third PVR measurements (P=0.107). On the other hand, significant differences were found between groups I and II and between groups I and III (P<0.05) in the three PVR measurements. Nevertheless, there was no significant difference between groups II and III in the three PVR measurements (P=0.204, 0.56, and 0.487 for the first, second, and third PVR measurements, respectively). Conclusion: A bladder ultrasound must be performed and interpreted carefully to avoid further unnecessary medications, investigations, or procedures. We recommend a second PVR measurement in patients with bladder outlet obstruction. Also, it is suggested to conduct similar studies in different conditions to confirm our findings.

Increased Urinary Adenosine Triphosphate in Patients With Bladder Outlet Obstruction Due to Benign Prostate Hyperplasia.

BACKGROUND: Diagnosis of bladder outflow obstruction (BOO) in patients with lower urinary tract (LUT) symptoms is challenging without using invasive urodynamic tests. Recently, we showed in vitro that urothelial strips from patients with benign prostatic hyperplasia (BPH) release more ATP than controls. Here, we tested whether urinary ATP can be used as a wall tension transducer non-invasive biomarker to detect BOO in patients with BPH. METHODS: 79 male patients with BOO and 22 asymptomatic controls were recruited prospectively. Patients were asked to complete the International Prostate Symptom Score (IPSS) questionnaire and to void at normal desire into a urinary flowmeter; the postvoid residual volume was determined by suprapubic ultrasonography. Urine samples from all individuals were examined for ATP, creatinine, and lactate dehydrogenase. RESULTS: BOO patients had significantly higher (P < 0.001) urinary ATP normalized by the voided volume (456 ± 36 nmol) than age-matched controls (209 ± 35 nmol). Urinary ATP amounts increased with the voided volume, but the slope of this rise was higher in BOO patients than in controls. A negative correlation was detected between urinary ATP and flow rate parameters, namely maximal flow rate (r = -0.310, P = 0.005), Siroky flow-volume normalization (r = -0.324, P = 0.004), and volume-normalized flow rate index (r = -0.320, P = 0.012). We found no correlation with LUT symptoms IPSS score. Areas under the receiver operator characteristics (ROC) curves were 0.91 (95%CI 0.86-0.96, P < 0.001) for ATP alone and 0.88 (95%CI 0.81-0.94, P < 0,001) when adjusted to urinary creatinine. CONCLUSIONS: Patients with BOO release higher amounts of ATP into the urine than the control group. The high area under the ROC curve suggests that urinary ATP can be a high-sensitive non-invasive biomarker of BOO, which may have a discriminative value of detrusor competence when comparing BPH patients with low urinary flow rates. Prostate 76:1353-1363, 2016. © 2016 Wiley Periodicals, Inc.

The association of urinary nerve growth factor levels with bladder outlet obstruction in women.

OBJECTIVES: Nerve growth factor (NGF) has been proposed as a urinary biomarker and previously shown to be elevated in male patients with bladder outlet obstruction (BOO) and other lower urinary tract symptoms. No published studies have examined NGF as a potential urinary biomarker in women with BOO. The aims of this prospective study were to evaluate NGF levels in urine from women with anatomic BOO resulting from pelvic organ prolapse (POP) and/or previous incontinence surgery and to measure the effect associated with surgical or conservative management. METHODS: From January to September 2012, all female patients referred for evaluation and management of BOO from POP or previous incontinence surgery were screened for enrollment. Inclusion criteria included elevated postvoid residual, valsalva voiding on urodynamics, or urinary peak flow (Qmax) of 12 mL/s or less. A control group of 10 asymptomatic age-matched female volunteers was also recruited. In all subjects, urinary NGF and creatinine (Cr) levels were measured and normalized to the urinary Cr concentrations (NGF/Cr). Urinary NGF levels were measured at 1 month and 3 months after either surgical correction or initiation of clean intermittent catheterization. RESULTS: A total of 10 female patients with anatomic BOO (mean [SD] age of 66.2 [3.88] years) and 10 female control subjects (mean [SD] age of 62 [7] years) were recruited. Nine patients had POP. Six patients had undergone a previous anti-incontinence procedure. Five patients had both POP and undergone a previous anti-incontinence procedure. The urinary NGF/Cr levels in the study patients with BOO (mean [SE] 20.8 [4.31] pg/mg) were significantly higher (P = 0.0001) than the levels in the age-matched control group (5.6 [0.65] pg/mg). After treatment, the urinary NGF/Cr level significantly decreased to 6.50 (0.57) pg/mg (P = 0.01) CONCLUSIONS: In this study, female patients with anatomic BOO resulting from POP and/or previous incontinence surgery had significantly higher urinary NGF/Cr levels when compared with age-matched controls. After treatment, the urinary NGF/Cr levels significantly decreased.

Urine neutrophil gelatinase-associated lipocalin identifies unilateral and bilateral urinary tract obstruction.

BACKGROUND: Urinary tract obstruction (UTO) is a common problem that can lead to permanent loss of kidney function. Unilateral UTO may be difficult to diagnose. Urinary neutrophil gelatinase-associated Lipocalin (uNGAL) may identify unilateral and bilateral UTO. METHODS: Retrospective case-control study of patients undergoing hospital admission at three sites. UTO was determined by review of medical records and cases were matched to control patients. uNGAL was measured by immunoblot. RESULTS: Twenty-four unilateral UTO and 15 bilateral UTO cases were identified. Admission serum creatinine (sCr) (milligram per decilitre) was significantly higher in bilateral UTO, 2.0 (1.1-5.3), but not unilateral UTO, 1.1 (0.8-1.5), compared to controls, 0.9 (0.8-1.2). uNGAL (nanogram per millilitre) was significantly higher both in patients with bilateral UTO, 140 (40-450), and unilateral UTO, 50 (20-100), compared to controls, 20 (10-45). DISCUSSION: uNGAL identifies kidney injury in unilateral and bilateral UTO even in the absence of an elevated sCr.

[Association between residual urinary volume and urinary tract infection: prospective trial in 225 male patients]. / Assoziation zwischen Restharnvolumen und Harnwegsinfektion : Prospektive Studie an 225 Männern.

PURPOSE: Urinary tract infections can result from bladder outlet obstruction and consecutive post-void residual urine. In a recent publication, a cutoff for post-void residual urine of 180 ml was calculated, revealing sensitivity and specificity of 87 and 98.5%, respectively, regarding occurrence of significant bacteriuria in asymptomatic men. In the present study the association between post-void residual urine volume and urinary tract infection was evaluated, and different cutoff values were validated. MATERIALS AND METHODS: A total of 225 asymptomatic patients (median age 66 years) were prospectively evaluated regarding the following criteria: prostate-specific antigen, prostate volume, International Prostate Symptom Score, peak urinary flow rate, urine culture results, urinary test strip, and post-void residual urine volume. By ROC analysis a cutoff predicting significant bacteriuria was calculated, and different cutoff values were validated. The independent influence of several parameters on the incidence of urinary tract infection was measured using multivariate regression analyses. RESULTS: Of the patients, 60% were able to completely empty the bladder (post-void residual urine volume

Increased urinary nerve growth factor as a predictor of persistent detrusor overactivity after bladder outlet obstruction relief in a rat model.

PURPOSE: We evaluated urinary nerve growth factor as a predictive factor for persistent detrusor overactivity after bladder outlet obstruction relief in a rat model. MATERIALS AND METHODS: A total of 50 female Sprague-Dawley(R) rats were divided into 2 groups, including 10 sham operated controls and 40 with bladder outlet obstruction. Obstruction was induced by partial urethral ligation and relieved by ligation removal after 3 weeks. Voided urine was collected before bladder outlet obstruction at time 1, 3 weeks after obstruction onset at time 2 and 3 weeks after obstruction relief at time 3. Cystometry was done in awake rats at times 2 and 3. Bladder tissue was harvested at time 3. Urinary and bladder tissue nerve growth factor was measured by enzyme-linked immunosorbent assay with results adjusted based on creatinine concentration. RESULTS: In 16 rats in which detrusor overactivity disappeared after bladder outlet obstruction relief (group 1) urinary nerve growth factor/creatinine significantly increased from time 1 to 2 and significantly decreased from time 2 to 3 (p = 0.001 and 0.003, respectively). In 8 rats with persistent detrusor overactivity despite obstruction removal (group 2) urinary nerve growth factor/creatinine significantly increased from time 1 to 2 but did not change from time 2 to 3 (p = 0.012 and 0.123, respectively). These rats with persistent detrusor overactivity also had significantly higher urinary nerve growth factor/creatinine at time 1 than controls and group 1 (p = 0.015 and 0.005, respectively). CONCLUSIONS: Changes in urinary nerve growth factor may reflect detrusor overactivity, as diagnosed on 2 consecutive cystometries. Increased urinary nerve growth factor before bladder outlet obstruction may predict persistent detrusor overactivity after obstruction relief.

Urinary nerve growth factor levels are increased in patients with bladder outlet obstruction with overactive bladder symptoms and reduced after successful medical treatment.

OBJECTIVES: Urinary nerve growth factor (NGF) levels have been shown to be increased in patients with symptoms of overactive bladder (OAB). This study was designed to measure the urinary NGF levels in patients with bladder outlet obstruction (BOO) with or without OAB and to determine whether urinary NGF can serve as a biomarker for OAB. METHODS: Urinary NGF levels were measured in 38 male control subjects without lower urinary tract symptoms and 153 patients with BOO. The diagnosis of BOO was further classified as BOO/non-OAB (n = 21), BOO/OAB (n = 25), BOO with urodynamically confirmed detrusor overactivity (BOO/DO, n = 47), and BOO/OAB in patients who had received successful medical treatment (n = 60). The urinary NGF levels were measured by enzyme-linked immunosorbent assay and compared among the different groups. The total urinary NGF levels were normalized to the concentration of the urinary creatinine (NGF/Cr) level. RESULTS: The urinary NGF/Cr levels were very low in the control group (mean +/- standard error 0.005 +/- 0.003) and in patients with BOO/non-OAB (0.017 +/- 0.009) and significantly greater in patients with BOO/OAB (0.81 +/- 0.31) and BOO/DO (0.80 +/- 0.13). The urinary NGF/Cr levels were not significantly different between the BOO/OAB and BOO/DO groups; however, the urinary NGF/Cr levels returned to normal levels (0.059 +/- 0.021) after successful relief of OAB symptoms with medical treatment. CONCLUSIONS: In our study, patients with BOO/OAB or BOO/DO had significantly greater urinary NGF/Cr levels compared with controls. These levels decreased to normal after successful relief of OAB symptoms. These results suggest that urinary NGF could be a potential biomarker for BOO with symptoms of OAB.

Correlation of urinary nerve growth factor level with pathogenesis of overactive bladder.

AIMS: The origin of overactive bladder (OAB), which is a leading cause of lower urinary tract symptoms, remains unknown. Nerve growth factor (NGF) is one of the neurotrophic factors which are needed for the maintenance of sensory neurons. It is known that too much expression of NGF may induce bladder hyperactivity. In this study, we explored the correlation of the level of urinary NGF with various pathogenic OAB such as idiopathic, neurogenic OAB, and bladder outlet obstruction (BOO). METHODS: The study group included 51 OAB patients. Thirteen patients (7 females and 6 males) had idiopathic detrusor overactivity (DO) without BOO, 6 female idiopathic OAB without DO (sensory urgency), 16 patients with BOO due to BPH, and 16 patients with neurogenic DO (10 due to spinal cord injury (SCI), 6 due to cerebrovascular disease (CVD)). Thirty-two patients who had normal cystometric findings (23 females and 9 males) without OAB symptoms were used as controls. Urinary NGF levels were measured by enzyme-linked immunosorbent assay technique (ELISA) and the results were normalized based on creatinine (Cr) concentration. RESULTS: The urinary NGF levels in patients with neurogenic DO due to SCI, BOO, and sensory urgency were significantly higher compared with those of normal cystometric finding patients. However, the levels of urinary NGF were not statistically significant between patients with idiopathic DO without BOO, neurogenic DO due to CVD and patients with normal cystometric findings. CONCLUSIONS: These data suggest that urinary NGF levels could serve as a basis for adjunct diagnosis of OAB.

Is the short-term outcome of transurethral resection of the prostate affected by preoperative degree of bladder outlet obstruction, status of detrusor contractility or detrusor overactivity?

AIM: The aim of this study was to investigate whether the preoperative degree of bladder outlet obstruction (BOO), detrusor underactivity (DUA) or detrusor overactivity (DO) affected the short-term outcome of transurethral resection of the prostate (TURP) for patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (LUTS/BPH). METHODS: Ninety-two patients with LUTS/BPH aged 50 years or older who were considered to be appropriate candidates for TURP were included in this study. Pressure-flow study and filling cystometry were performed to determine BOO, DUA and DO before TURP. The efficacy of TURP was determined at 3 months after surgery using the efficacy criteria for treatment of BPH assessed by the International Prostate Symptom Score, QOL index, maximum flow rate and postvoid residual urine volume. RESULTS: On preoperative urodynamics, 60%, 40% and 48% of patients showed BOO, DUA and DO, respectively. After TURP, 76% showed 'excellent' or 'good' overall efficacy, whereas only 13% fell into the 'poor/worse' category. The efficacy was higher as the preoperative degree of BOO worsened. In contrast, neither DO nor DUA influenced the outcome of TURP. However, the surgery likely provided unfavorable efficacy for patients having DO but not BOO. Only 20% of the patients who had both DO and DUA but did not have BOO achieved efficacy. CONCLUSIONS: Transurethral resection of the prostate is an effective surgical procedure for treatment of LUTS/BPH, especially for patients with BOO. DUA may not be a contraindication for TURP. The surgical indication should be circumspect for patients who do not have BOO but have DO.

The utility of fetal urine biochemistry in the management of lower urinary tract obstructions. A report of 3 cases.

The aim of this study is to implement the use of biochemical parameters in the analysis of fetal urine to assist with decision making for surgical intervention for fetal obstructive uropathy. Three patients were selected over a 6 month period following ultrasound diagnosis of megabladder and oligohydramnios. Amniocentesis and cystocentesis were performed for karyotyping and biochemical urinary electrolyte evaluation, respectively. Fetal urine biochemistry assisted in decision making with regard to patient and fetal well being. In each of the cases the parameter cutoffs were diagnostic of fetal condition. While the long term benefits of fetal intervention for obstructive uropathy are still debated, we feel that the use of urine biochemical criterIa provide the best current method to select the subjects to be submitted to vesicoamniotic shunt centres.

Urinary transforming growth factor-beta1 levels correlate with bladder outlet obstruction.

BACKGROUND: Urinary transforming growth factor-beta1 (TGF-beta1) levels have been shown to correlate with elevated intrapelvic pressure associated with ureteropelvic junction obstruction. Other studies have evaluated urinary TGF-beta1 levels in prostate cancer. This study tests the hypothesis that urinary TGF-beta1 levels might correlate with objective measures of bladder outlet obstruction (BOO). METHODS: Twenty-three men (age: 46-85 years) with lower urinary tract symptoms underwent urodynamic studies consisting of non-invasive uroflowmetry, cystometrogram and voiding pressure flow studies. Patients were classified as obstructed (n = 17) or not obstructed (n = 6) based on Abrams-Griffith nomograms. Urinary TGF-beta1 was extracted from an aliquot of urine obtained at the time of bladder catheterization for urodynamic studies. Urinary TGF-beta1 levels were then determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: There was a strong correlation between urinary TGF-beta1 levels and the presence of obstruction by Abrams-Griffith nomogram criteria (P = 0.025). Urinary TGF-beta1 levels were significantly higher in men with obstruction (0.039 +/- 0.011 pg/mL) than in men without obstruction (0.029 +/- 0.009 pg/mL; P = 0.036). CONCLUSION: Urinary TGF-beta1 levels correlate with objective measures of BOO. Further study is needed to test the utility of urinary TGF-beta1 as a non-invasive diagnostic tool for BOO.

The response of the fetal kidney to obstruction.

In a fetal ovine model the renal effects of different anatomic levels of fetal urinary obstruction were studied. Parameters of prenatal renal growth and differentiation were characterized and correlated with the patterns of renal response to in utero obstruction. Complete ureteral or urethral obstruction was produced in the sheep fetus at 55 to 60 days of gestation. Animals were delivered and sacrificed at near term (140 days), and the kidneys were removed and prepared for analysis. Parameters examined included weight, histology, glomerular number and total surface area, as well as urinary sodium, creatinine, osmolarity and N-acetyl glucosaminidase. Three patterns of response were identified, producing hydronephrotic, cystic or dysgenetic kidneys. Hydronephrotic kidneys were usually the result of bladder outlet obstruction or ureteral obstruction with spontaneous urinary decompression. These kidneys were large (20.7 gm. versus normal 10.8 gm., p less than 0.0001), with thinning of cortical parenchyma that was structurally intact. Glomerular number and surface area were normal. Cystic kidneys were large (14.2 gm., p less than 0.05) with grossly visible cysts and an effaced medulla. Cortical structure was distorted by cysts but basic elements were intact. Glomerular number and surface area were not reduced. Dysgenetic kidneys were small (3.9 gm., p less than 0.0001) with markedly abnormal cortical structure and little recognizable medulla. Histological elements similar to fetal structures were present, including cuboidal/columnar tubular epithelium and peritubular mesenchymal collars. Glomerular number and surface area were significantly less than normal (p less than 0.001). The kidneys contralateral to unilaterally obstructed kidneys were significantly larger than normal (16.2 gm., p less than 0.0001), with normal histology, glomerular number and surface area, indicating in utero contralateral renal hypertrophy. Urinary sodium was variably affected in the hydronephrotic kidneys and was identical to plasma in the dysgenetic kidneys. These results indicate the technical feasibility of in utero models of urinary obstruction. Renal growth and patterns of differentiation were markedly affected by in utero obstruction. They should be a major focus in the investigation of congenital obstructive uropathy, since normal processes of renal growth and differentiation form the basis for postnatal function.

Fetal urinary electrolytes in bladder outlet obstruction.

Ultrasound findings and urinary electrolytes in the fetus were correlated with fetal outcome and postmortem findings in 8 cases of fetal bladder outlet obstructions. One of the two fetuses, suggesting normal renal function according to urinary electrolytes, displayed renal dysplasia at birth. Six fetuses were predicted to have poor renal function, 5 of these were found to have renal dysplasia at autopsy. The interpretation of fetal urinary electrolytes as a prognostic indication for the presence or absence of renal dysplasia needs to be clarified.