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The relief of the impediment to urinary flow is the treatment of acute kidney failure due to urinary tract obstruction. However, there is a risk of inducing massive polyuria, which can be self-limited or produce severe contraction of the intravascular volume with pre-renal acute kidney failure and alterations in the internal environment. Polyuria, urine output > 3 L/d or > 200 mL/min for more than 2 hours, can have multiple causes, and can be classified as osmotic, aqueous or mixed. Post-obstructive polyuria obeys different pathogenic mechanisms, which overlap and vary during a patient's evolution. Initially, there is a decrease in vasoconstrictor factors and an increase in renal blood flow, which, added to the excess of urea accumulated, will cause intense osmotic diuresis (osmotic polyuria due to urea). Added to these factors are the positive sodium and water balance during acute renal failure, plus the contributions of crystalloid solutions to replace diuresis (ionic osmotic polyuria). Finally, there may be tubular dysfunction and decreased solutes in the renal medullary interstitium, adding resistance to the action of vasopressin. The latter causes a loss of free water (mixed polyuria). We present the case of a patient with post-obstructive polyuria where, by analyzing the clinical symptoms and laboratory alterations, it was possible to interpret the mechanisms of polyuria and administer appropriate treatment for the pathogenic mechanism.

Anterior urethral valves are a rare cause of obstructed voiding in adolescent children and are often unheard by adult urologists. In this case report, we discuss the management of two adolescent patients who were referred to us with obstructive voiding symptoms with a diagnosis of neurogenic bladder and posterior urethral valves respectively but on evaluation were found to have anterior urethral valves. This article highlights the need for considering anterior urethral valve as an important differential diagnosis in children and adolescents presenting with obstructive voiding symptoms so as to avoid delay in diagnosis and management in young boys., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Obstructive voiding disorder (OVD) occurs during aging in men and is often, but not always, associated with increased prostate size, due to benign prostatic hyperplasia (BPH), prostatitis, or prostate cancer. Estrogens are known to impact the development of both OVD and prostate diseases, either during early urogenital tract development in fetal-neonatal life or later in adulthood. To examine the potential interaction between developmental and adult estrogen exposure on the adult urogenital tract, male CD-1 mice were perinatally exposed to bisphenol A (BPA), diethylstilbestrol (DES) as a positive control, or vehicle negative control, and in adulthood were treated for 4 months with Silastic capsules containing testosterone and estradiol (T+E2) or empty capsules. Animals exposed to BPA or DES during perinatal development were more likely than negative controls to have urine flow/kidney problems and enlarged bladders, as well as enlarged prostates. OVD in adult T+E2-treated perinatal BPA and DES animals was associated with dorsal prostate hyperplasia and prostatitis. The results demonstrate a relationship between elevated exogenous estrogen levels during urogenital system development and elevated estradiol in adulthood and OVD in male mice. These findings support the two-hit hypothesis for the development of OVD and prostate diseases.

Purpose: We studied the effect of oxybutynin on bladder and upper urinary tract outcomes in infants following posterior urethral valve ablation., Materials and Methods: Patients younger than 12 months old who had undergone primary endoscopic valve ablation for posterior urethral valves were screened for eligibility. Patients who had undergone urinary diversion or had other conditions that could affect lower urinary tract function were excluded. Study patients were randomized to either oxybutynin (0.2 mg/kg 3 times daily) until toilet training or active observation. The study end points were serum creatinine, estimated glomerular filtration rate, hydronephrosis improvement, vesicoureteral reflux resolution, febrile urinary tract infection and toilet training., Results: A total of 49 infants (24 receiving oxybutynin and 25 undergoing observation) were enrolled between December 2013 and September 2015 and completed at least 1 year of followup. Oxybutynin was discontinued before toilet training in 5 patients due to facial flushing in 2, bladder and upper tract dilatation in 2, and cognitive changes in 1. After a median followup of 44.2 months (range 12 to 57.6) median serum creatinine and estimated glomerular filtration rate were not significantly different between the groups (p=0.823 and p=0.722, respectively). Renal units in the oxybutynin group had a greater likelihood of hydronephrosis improvement (61.9% vs 34.8%, p=0.011) and resolution of vesicoureteral reflux (62.5% vs 25%, p=0.023). Febrile urinary tract infection (29.2% vs 40%, p=0.404), completion of toilet training (70.8% vs 76%, p=0.748) and age at toilet training (p=0.247) did not differ significantly between the oxybutynin and observation groups., Conclusions: Oxybutynin enhances hydronephrosis improvement and vesicoureteral reflux resolution following primary endoscopic valve ablation in infants but periodic monitoring is warranted.

Introduction: Nomograms using the VBN model of women micturition allowed evaluating detrusor contractility (k) and urethral obstruction (U) from pressure-flow (PFs) recordings. While the model worked for most of the patients, an intriguing result, negative U value was observed for patients with high flow-low detrusor pressure (Qp voids). To explain that condition, our hypothesis was a weak urethral resistance to dilatation or increased expansibility (URD)., Methods: The area offered to the fluid at each point of the urethra (its dilatation) is a function of the time depending difference between inside and outside pressures. In the VBN model, this function is sigmoid-like, the same for all women. For Qp voids, Q recorded was more higher than it would be with the recorded pressure (VBN analysis). So, modeling allowed computing abnormally increased urethral wall expansibility (URD) whose consequence would be an increased flow., Results: Among 222 non-neurologic women referred for investigation of various lower urinary tract symptoms, 27 (mean age 66.3±11.4 y) had Qp void: Q max =27±6mL/s; p det.Qmax =7.5±4.7cm H 2 O. Mean URD value was .36±.67. Introduction of URD in a modeled analysis of urodynamic traces led to a good fitting between recorded and computed traces for the 27 Qp., Conclusion: Mathematical modeling of micturition allows proposing an explanation of the unexpected observations of Qp voids. They would be due to abnormal urethral wall elasticity. Despite major challenges measurement of this elasticity would be the next step., Level of Evidence: 3., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objectives: Cardiac remodeling due to renal dysfunction may have an impact on myocardial function (MF) of fetuses with lower urinary tract obstruction (LUTO). The aim was to identify possible differences in MF in LUTO fetuses compared with healthy controls and to look for interactions between urine biochemistry and MF indices., Methods: This is a cohort study consisting of 31 LUTO fetuses and 45 healthy controls. Subgroups were generated according to intrauterine therapy (group 1: LUTO after therapy, group 2: LUTO without therapy at the time of examination, and group 3: controls). MF indices were measured using pulsed wave tissue Doppler imaging and M-mode. Furthermore, results of fetal urine biochemistry were gathered retrospectively., Results: Among other findings, right ventricular (RV) e'/a' ratio was lower in group 1 compared with group 3 (p = .050). According to gestational age (GA) level-dependent analysis, RV isovolumetric relaxation time was significantly longer in group 2 compared with group 1 and group 3 at GA level 1 (19 wk of gestation). A significant positive correlation between RV e'/a' ratio and β-2-microglobulin as well as α-1-microglobulin and potassium could be observed., Conclusion: We observed differences in MF and an association between ventricular filling pattern and renal protein secretion in LUTO fetuses. This can be interpreted as a sign of intrauterine cardiac remodeling., (© 2019 John Wiley & Sons, Ltd.)

Introduction: A posterior urethral valve (PUV) may lead to extravasation of urine, resulting in prenatal ascites and/or perirenal urinoma. Extravasation has been presumed to act as a pop-off mechanism, preserving renal function, but previous reports addressing this presumption have been inconclusive., Aim of Study: The present study compares renal function in patients with PUV with and without extravasation., Material and Methods: Sixty boys with a confirmed diagnosis of PUV as neonates (gestational age [GA]<44 weeks) throughout 2001-2016 were included. Clinical data were collected from medical records. Renal function was assessed by nadir plasma creatinine, creatinine at the last follow-up, and glomerular filtration rate (GFR) at the last follow-up. The GFR was estimated using the Schwartz formula. Renal function was classified according to the kidney disease: improving global outcomes (KDIGO) guidelines' grades of chronic kidney disease (CKD). Glomerular filtration rate > 90 ml/min/1.73m 2 at the last follow-up was classified as normal renal function., Results: Twelve patients (20%) had ascites and/or urinoma, and 48 (80%) did not. GA and birth weight were not different in patients with and without extravasation. PUV was suspected from prenatal ultrasound findings in 66.7% of the patients in both groups. Median nadir creatinine was 21 (range, 11-33) μmol/L in boys with ascites/urinoma, and all values were within the age-adjusted reference values. Nadir creatinine was 23 (14-199) μmol/L in boys without extravasation, and it was above the normal range in 14 boys. The incidence of elevated nadir creatinine was significantly different in the two groups (p < 0.025). One of the 12 patients with extravasation developed chronic renal failure (CKD 3). In the group of 48 patients without extravasation, 20 (42%) had chronic renal failure grade 2-5, and among these, 5 patients have had a renal transplant (CKD grade 5). The prevalence of CKD grade 2-5 was statistically different in the two groups (p = 0.03). These findings are presented in the summary figure., Conclusion: Extravasation of urine was found in 12 of 60 (20%) boys with PUV. These patients had significantly lower prevalence of CKD at the last follow-up than patients without extravasation. This finding is important in prenatal counseling. It also indicates that prenatal decompression of the bladder and upper tract is beneficial in patients with PUV, which is relevant to the discussion of prenatal intervention in these fetuses., (Copyright © 2019 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.)

Objective: Our objective was to evaluate bladder outlet obstruction (BOO) consequences on the detrusor activity, to analyze the impact of medical and surgical treatments, and to study the reasons for recurrence of urinary symptoms after surgical treatment., Method: A non-systematic review of the scientific literature was conducted from the PubMed database to retrieve the most relevant scientific publications between 2000 and July 2018 with the keywords: BPH, bladder obstruction, bladder instability, surgery, and reoperation. A first research was crossed with the results of the reviews of literature already published and was enriched by the contributions of the various authors. A synthesis has been proposed., Results: The consequences of bladder outlet obstruction (BOO) on the detrusor may be detrusor overactivity (DOA) or detrusor hypocontractility. DOA is found in about 50% of patients at the time of their surgery and its evolution is most often favorable after surgical treatment (resolved or reduced in 2/3 of cases). Bladder hypocontractility is responsible for acute or chronic urinary retention. It can be the cause for poor postoperative micturition recovery requiring self-catheterization which the patient must have been informed before surgical treatment. Surgery reduces urinary symptoms with a low but significant surgical revision rate (10 to 30% depending on the surgical technique). The less efficient technique with regard to surgical revision rates are prostatic radiofrequency or cervico-prostatic incision, followed by laser vaporization techniques, TURP and adenomectomy (surgical or endoscopic). Adenomectomy is the surgical technique that has the lowest recurrence rate. The identified risk factors for surgical revision are the surgeon's experience, the power of the laser (in case of photovaporization), the surgical technique employed, the length of operative time, the low or excessive volume of the prostate, the significant pre-operative post-void residual volume, and the slight decrease of postoperative PSA level. Prior to any surgical revision for recurrence of urinary symptoms, the assessment should include the review of previous surgical report, the evaluation of the resected prostatic volume and the residual prostatic volume, the IPSS score, the calendar of micturition, the urethrocystoscopy and the urodynamic assessment., Conclusion: BOO can lead to bladder dysfunction such as DOA or detrusor hypocontractility. Resolution of BOO by a suitable surgical treatment allows, in the majority of the cases, to resolve bladder dysfunctioning. In case of failure, the assessment must be complete to define the causes and to find the most suitable solution., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Posterior urethral valves (PUV) constitute a significant urological cause of chronic kidney disease (CKD) in children. The condition is characterised by the unique pathophysiology of the evolution of bladder dysfunction after relief of obstruction, which contributes to CKD. Improvements in prenatal diagnosis followed by selective foetal intervention have not yet produced improvement in long-term renal outcomes, although better patient selection may alter this in the future. Proactive management with surveillance, pharmacotherapy, timed voiding, double voiding, and/or assisted bladder-emptying, is being increasingly offered to those with severe bladder dysfunction and has the potential of reducing the burden of renal disease. Clinicians are currently able to counsel regarding the prognosis using serum creatinine and other emerging markers. However, much of this work remains to be validated. Satisfactory graft survival rates are now reported with aggressive management of bladder dysfunction in children who are candidates for renal transplantation. Knowledge gaps exist in identifying early markers of renal injury, risk stratification, and in understanding patient and carer perspectives in PUV.

Introduction: Congenital Lower Urinary Tract Obstructions (LUTO) is a heterogeneous group of diseases in which urine elimination is obstructed at the level of bladder neck or urethra. The aim of the study is to evaluate the long-term renal outcome of patients suffering of congenital LUTO., Patients and Method: We retrospectively reviewed patients with congenital LUTO. All patients had at least 1 year follow-up. Data on surgery, renal imaging and Schwartz estimate creatinine clearance were collected. Incidence of Chronic Renal Disease (CRD) is presented with Kaplan-Meier method., Results: 40 patients were included, 23 patients with Posterior Urethral Valve (PUVs) and 17 patients with other aetiologies: anterior urethral valve (2), urethral atresia (2), urethral stenosis (2), cloacal malformations (2), obstructive ureterocele (1), bladder trigone malformation (1) and neonatal bladder-sphincter dysfunction without neurological abnormalities (7). Incidence of CRD at age 10 years was 37% in congenital LUTO, 42% in PUVs and 30% in other aetiologies, and was significantly higher in PUVs (P=0.032). Renal prognosis was significantly worsened by discover of retentional bladder wall changes in initial cystoscopy, and by loss of parenchymal differentiation or cortical microcysts in first ultrasonography. The use of urinary diversion was significantly higher in LUTO of other aetiologies., Conclusion: A high incidence of CRD is observed in patients with congenital LUTO, significantly higher in patients with PUV. LUTO of other aetiologies require step by step surgical management and higher use of urinary diversion. Precise initial evaluation in cystoscopy and ultrasonography is required and participate to evaluate future renal outcome., Level of Incidence: 4., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Aims: It was demonstrated earlier that reduced maximum flow-rate (Q max ) during intubated flow (IF) in women may be the consequence of a urethral reflex. Over-estimation of outflow obstruction is the consequence. Our hypothesis, that a similar phenomenon could occur in men, is tested using results of a free uroflow (FF) preceding an IF to eventually correct the Abrams-Griffiths (AG) number., Methods: Retrospectively, analysis of 441 urodynamic studies of men suspected of bladder outflow obstruction (BOO) was performed. The Valentini-Besson-Nelson model links outflow obstruction (parameter pucp) and the detrusor contractility (parameter k) to Q max and detrusor pressure at Q max (p det.Qmax ). AG and pucp are strongly correlated. Contractility is described by a graphical representation (a nomogram) which numerical fitting is an algebraic equation f(Q max ,p det.Qmax ). Nomograms based on IF allowed computing a calculated AG (corr-AG) on the basis of free flow., Results: Included files (N = 362) had filling volume during FF > 90 mL; corr-AG was compared to AG. When Q max.FF  > 1.5*Q max.IF (N = 114), 61 patients (53.5%) were found less obstructed with corr-AG, no one more obstructed. Increased BOO could be the result of a urethral reflex during IF and AG gave an overestimation. When Q max.FF  < 1.5*Q max.IF (N = 248), only 39 patients (12.1%) were found less obstructed with corr-AG and 28 (11.3%) more obstructed., Conclusion: To obtain a reliable evaluation of BOO in men, it is suitable to perform a FF before IF. A corrected AG (corr-AG) obtained from IF analysis and nomograms based on FF may be helpful for evaluation of BOO in men., (© 2017 Wiley Periodicals, Inc.)

Aims: To design a simple office-based method to evaluate characteristic parameters from free uroflowmetries (FF) or pressure flow studies (PFs). This method can be applied by any physician to any recording, for instance in the follow-up of women at risk of developing outflow obstruction over time after surgical interventions., Method: Using pressure-flow studies (PFs), a reliable evaluation of urethral obstruction (U) and detrusor contractility (k) parameters could be obtained from the maximum flow rate and detrusor pressure at maximum flow rate. Nomograms for these parameters were derived from theoretical computations using the VBN model. Then, to allow an evaluation of the real urethral obstruction, a protocol was designed incorporating FF data in the follow-up of women suspected of urethral obstruction., Results: Two nomograms were obtained: (1) A urethral obstruction nomogram allowing to define a Woman Obstruction Index (WOI = p det.Qmax - 0.5*Q max ) which has the same structure than the A-G number in men. (2) A detrusor contractility nomogram which was generalized to all initial bladder volumes. The curves were fitted by algebraic equations easily programmable on any handheld device., Conclusion: Using a mathematical model of micturition and data extracted from PFs, two nomograms on urethral obstruction and detrusor contractility were designed. This tool offers a rapid and practical method for the clinician to follow women at risk of obstruction over time. Its applications will be the purpose of further studies. Neurourol. Urodynam. 36:37-42, 2017. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Objective: To assess the long-term impacts of bladder neck incision (BNI) on continence and ejaculatory function of adults who underwent concurrent posterior urethral valve (PUV) ablation and BNI during childhood., Materials and Methods: A retrospective chart review was performed to find all adult patients with relevant history. All patients had undergone BNI at 6 o'clock proximal to the verumontanum with caution to leave the adventitia and verumontanum untouched. Charts were reviewed and attempts were made to contact those ≥18 years old for follow-up. Patients were specifically evaluated for lower urinary tract symptoms and ejaculatory condition., Results: Among patients treated for PUV between 1998 and 2015 in our center, 21 were ≥18 years old at the time of assessment. Until February 2016, we were able to contact 18 patients, all of whom agreed to participate. Mean age was 21.1 ± 2.9 years with a mean follow-up of 12.5 ± 4.8 years. None of those contacted had incontinence or dry ejaculations. All considered their ejaculations normal and only one complained of weak ejaculations. Four of 5 patients who consented to perform a semen analysis had normal tests and 1 had low sperm count with abnormal motility., Conclusion: BNI is not associated with additional risk of incontinence and dry ejaculation in early adulthood and preserves antegrade ejaculation. Concomitant valve ablation with BNI may provide additional benefits in care of PUV children, especially those with prominent bladder neck and poor bladder function at presentation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Rett Syndrome (RTT) is a neurodevelopmental disorder characterized by loss of acquired skills during development, autonomic dysfunction, and an increased risk for premature lethality. Clinical experience identified a subset of individuals with RTT that present with urological dysfunction including individuals with frequent urinary tract infections, kidney stones, and urine retention requiring frequent catheterization for bladder voiding. To determine if urologic dysfunction is a feature of RTT, we queried the Rett Syndrome Natural History Study, a repository of clinical data from over 1000 individuals with RTT and found multiple instances of urological dysfunction. We then evaluated urological function in a mouse model of RTT and found an abnormal pattern of micturition. Both male and female mice possessing Mecp2 mutations show a decrease in urine output per micturition event. Furthermore, we identified signs of kidney failure secondary to urethral obstruction. Although genetic strain background significantly affects both survival and penetrance of the urethral obstruction phenotype, survival and penetrance of urethral obstruction do not directly correlate. We have identified an additional phenotype caused by loss of MeCP2, urological dysfunction. Furthermore, we urge caution in the interpretation of survival data as an endpoint in preclinical studies, especially where causes of mortality are poorly characterized., Competing Interests: The authors have declared that no competing interests exist.

The therapeutic effect of doxazosin (40 μg/kg/day over one month) on urinary bladder was examined in female rats with modeled chronic infravesical obstruction (IVO) produced by graduated mechanical constriction of the proximal urethral segment. In one month, IVO induced a pronounced vesical hypertrophy both in treated and untreated rats that manifested in increased bladder weight and capacity, the latter increment being pronouncedly greater in treated rats. In untreated IVO rats, infusion cystometry revealed elevated basal intravesical pressure of void bladder P 0 , markedly increased maximal (premicturitional) pressure P max , and increased amplitude of spontaneous oscillations of intravesical pressure ΔP det in filled bladder. Doxazosin produced no significant effect on P max rise during IVO, but prevented elevation of P 0 and increment of ΔP det in filled bladder. During gradual filling of urinary bladder in control (intact) rats, the parasympathetic vesical influences increased progressively, while in untreated IVO rats, the adrenergic influences prevailed even at maximal filling of the bladder. In IVO rats, doxazosin prevented the bias of the sympathetic-parasympathetic balance in the filled bladder in favor of sympathetic influences, but did not prevent this bias in a void bladder. It is hypothesized that α-adrenoblockers improve micturition during IVO caused by benign prostatic hyperplasia not only by decreasing the urethral resistance to urine flow due to down-regulation of prostate smooth muscle tone, but also by a direct action of these blockers on detrusor adrenergic receptors and central structures involved in urinary bladder control.

An antimuscarinic therapy may increase the risk of voiding dysfunction. However, it is unclear whether the relative risk of voiding dysfunction is different among antimuscarinics. Therefore we determined the potencies both in enhancing the bladder capacity (BC), effectiveness, and in decreasing the maximum urinary flow rate (Qmax), voiding dysfunction, to compare their therapeutic indices.Under urethane anesthesia, urinary flow rate was measured at distal urethra using an ultrasonic flow meter in female Sprague-Dawley rats with functional urethral obstruction induced by a continuous i. v. infusion of α1-adrenoceptor agonist A-61603 (0.03 μg/kg/min). In a separate group of urethane-anesthetized rats without urethral obstruction, an intermittent cystometry was performed to determine BC.Intravenous imidafenacin and oxybutynin produced a significant dose-dependent decrease in Qmax with the minimum doses of 0.03 and 1 mg/kg, respectively. Imidafenacin and oxybutynin markedly increased BC, with minimum doses of 0.01 and 3 mg/kg, respectively. At the minimum dose to increase BC, oxybutynin caused a significant increase in residual urine volume with a significant decrease in voiding efficiency, whereas imidafenacin had no influence on these values. The relative influence index, which is the ratio of the minimum influence dose between in decreasing of Qmax and in increasing of BC, of imidafenacin was 10 fold higher than that of oxybutynin.This study suggests that imidafenacin has a lower relative risk of voiding difficulty compared with oxybutynin in rats. These results provide new information that antimuscarinics may have varying degrees of impact on voiding difficulty., (© Georg Thieme Verlag KG Stuttgart · New York.)

We aimed to characterize and to explore a treatment for a condition in which male mice exhibited a solid bulge in the preputial area and an inability to breed. Twenty-seven mice from several animal housing institutions in Spain were included in this study for microbiological and pathological characterization of this condition. The condition mostly affected breeding animals and was associated with the C57BL/6J genetic background. A solid, yellowish-white substance was found inside the prepuce, which displaced the penis cranially, preventing its externalization and limiting the animal's capacity to breed. This pattern was almost identical to that of post-coital vaginal plugs, suggesting that the blocking substance originated from ejaculate. Opposite to what was suggested in previous publications, the penis was completely intact in all of the cases, with no signs of mutilation or wounds. Based on our findings, we developed a surgical technique to clear the prepuce and recover breeding performance, which we tested in 15 other mice with the condition. We eliminated the blocking substance and recurrence of the condition by surgically opening the prepuce, and most of the animals recovered fertility.

Objectives: We investigated the effect of the selective prostaglandin E2 EP2 receptor agonist CP-533,536 on voiding efficiency in rats with midodrine-induced functional urethral obstruction., Methods: The effect of CP-533,536 (0.03-0.3 mg/kg, intravenous [i.v.]) on urethral perfusion pressure (UPP) was investigated in anesthetized rats pre-treated with midodrine (1 mg/kg, i.v.), which forms an active metabolite that acts as an α1 -adrenoceptor agonist. The effect of CP-533,536 (0.03-0.3 mg/kg, i.v.) on cystometric parameters was also investigated in anesthetized rats. In addition, the effect of CP-533,536 (0.03-0.3 mg/kg, i.v.) on residual urine volume (RV) and voiding efficiency (VE) was investigated in conscious rats treated with midodrine (1 mg/kg, i.v.)., Results: CP-533,536 dose-dependently decreased UPP elevated by midodrine in anesthetized rats. In contrast, CP-533,536 did not affect maximum voiding pressure, intercontraction interval, or intravesical threshold pressure. In conscious rats, midodrine (1 mg/kg, i.v.) markedly increased RV and reduced VE. CP-533,536 dose-dependently ameliorated increases in RV and decreases in VE induced by midodrine., Conclusions: These results suggest that a selective EP2 receptor agonist could ameliorate the elevation of RV and improve the reduction of VE in rats with functional urethral obstruction caused by stimulation of α1 -adrenoceptors. The mechanism of action might be not potentiation of bladder contraction but rather preferential relief of urethral constriction., (© 2014 Wiley Publishing Asia Pty Ltd.)

Purpose: An obstructive urinary flow pattern is frequently seen after tubularized incised plate urethroplasty for hypospadias. However, the significance of this finding has not been determined and long-term results are few. We describe postoperative long-term uroflowmetry results after puberty in males who underwent tubularized incised plate urethroplasty in childhood., Materials and Methods: A total of 126 boys underwent tubularized incised plate urethroplasty for distal penile to mid shaft hypospadias at Queen Silvia Children's Hospital in Gothenburg between 1999 and 2003. Of the patients 48 were toilet trained at surgery. We report on 40 patients who had data available at 2 and 12 months postoperatively, 7 years postoperatively and at puberty (median age 15.0 years, range 13.7 to 17.1). Of the patients 31 had distal and 9 had mid penile hypospadias. Clinical examination, urinary medical history, uroflowmetry and ultrasound measuring residual urine were performed. Maximum urinary flow was correlated to age and voided volume, using Miskolc nomograms for comparison of percentiles., Results: At 1 year postoperatively 15 boys (37.5%) had normal urinary flow (above 25th percentile), compared to 16 (40%) at 7 years and 38 (95%) at puberty (p <0.0001). Improvement was significant in patients with distal (p <0.0001) and mid penile hypospadias (p = 0.008), as well as in patients who did (p = 0.0078) and did not undergo intervention (p <0.0001). During followup 5 patients underwent meatotomy due to obstructive symptoms and 4 underwent dilation. Three of these 9 patients had lichen sclerosus., Conclusions: There is great potential for normalization of urinary flow at puberty for boys with hypospadias treated with tubularized incised plate urethroplasty. Unless symptoms occur, a conservative approach seems preferable., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Introduction: Elderly men with multiple comorbidities may be unfit to undergo surgical management of benign prostatic obstruction (BPO). Permanent and temporary prostatic stents have been developed as an alternative to chronic indwelling catheters in men unfit for surgery., Materials and Methods: Herein we review the past and present literature on the role and effectiveness of prostatic stents in the treatment of BPO., Results: Permanent prostatic stents have largely been abandoned in North America due to unfavorable outcomes and improved technologies to allow for treatment of BPO. Currently, the temporary Spanner stent is the only available stent on the market, but its effectiveness has mostly been documented for temporary relief of tissue edema following minimal invasive ablative treatments for BPO., Conclusions: The advent of well-tolerated surgical treatments for BPO (KTP laser vaporization, bipolar TURP, urethral lift devices) has diminished the need for permanent prostatic stents. The temporary Spanner stent is an alternative to urethral catheter, but requires adequate detrusor function and can cause irritative symptoms.

Purpose: To evaluate the effect of pentoxifylline (PTX), a nonspecific type 4 phosphodiesterase inhibitor, on contractility of obstructed detrusor muscles., Methods: Sixty male Sprague-Dawley rats were randomized into three groups each containing 20 animals. The control groups included rats with induced BOO which received the solvent of PTX (drinking water), the sham group included rats with intact bladder outlet which received no treatment, and the treatment group was treated with PTX after induction of BOO. Four weeks after the operation and/or treatment, animals were killed and detrusor muscle of them was evaluated for contractility parameters., Results: Carbachol-induced detrusor muscle tension increased proportionally with concentration of carbachol. The maximum carbachol-inducing muscle tension was significantly higher in the sham group in comparison to the rats with BOO (P < 0.001). In the latter group, PTX treatment caused no significant improvement in the maximum carbachol-induced muscle tension compared to the control group. However, no significant difference was observed among the study groups concerning the pEC50 of carbachol (5.77 ± 0.10, 5.96 ± 0.64, and 5.84 ± 0.17 in the sham, control, and treatment groups, respectively). BOO resulted in a great but statistically non-significant (P = 0.074) decrease in electrically induced bladder contraction in comparison with the sham group. Treatment with PTX reversed this effect significantly (P = 0.023), and the obtained values were almost the same as those of the sham group., Conclusion: PTX improved detrusor muscle contractions in responses to electric stimulation in obstructed bladder. In contrast, no improvement was detected in contractile responses to the carbachol stimulation.

Aims: The Blaivas-Groutz nomogram defines voiding obstruction in women using Qmax from the NIF and the maximum detrusor pressure (Pdetmax ) from the PFS. The aim of this study was to understand the relationship between NIF and PFS maximum flow rates in women with stress incontinence., Methods: We analyzed the UDS of 597 women with stress-dominant urinary incontinence. Each subject underwent a NIF and then a PFS. Mixed model was used to test the hypothesis that the relationship between flow rates and voided volume (VV) were similar for NIF and PFS., Results: There were 452 subjects with both NIF and PFS studies that met the inclusion criteria and had max flow rate (Qmax ) for both NIF and PFS. The mean age was 53. Overall, higher VV were observed during PFS compared to NIF and subjects had higher Qmax with NIF compared to PFS. The relationship between Qmax and VV was significantly different between NIF and PFS (P < 0.004). At 200 ml, NIF Qmax was 14% higher than PFS Qmax and this difference increased to 30% at 700 ml., Conclusion: The difference between PFS Qmax and NIF Qmax increases as VV increase. As a result, values from PFS and NIF cannot be used interchangeably as has been suggested in the Blaivas-Groutz nomogram for obstruction in women., (© 2014 Wiley Periodicals, Inc.)

Purpose: The existence of an inhibitory rectovesical reflex elicited by noxious colorectal afferent input was previously documented in an isovolumetric cystometry model with a ligated urethra. We compared the effect of noxious colorectal distension on bladder cystometry with an open and a ligated urethra., Materials and Methods: We used female Sprague Dawley® rats anesthetized with urethane. The effect of noxious (60 mm Hg) colorectal distension on intermittent and continuous cystometry with an open urethra was studied and then compared to inhibiting isovolumetric bladder contractions in the same rat after ligating the urethra. We evaluated volume, the pressure micturition threshold, the intercontraction interval, bladder contraction frequency and amplitude of micturition contractions., Results: Noxious colorectal distension at 60 mm Hg did not significantly influence volume or the pressure micturition threshold during intermittent cystometry. It also did not influence the pressure micturition threshold, the intercontraction interval or bladder contraction frequency during continuous cystometry. After urethral ligation 60 mm Hg colorectal distension inhibited isovolumetric bladder contraction frequency in the same rat (mean ± SEM 0.363 ± 0.207 vs 0.886 ± 0.106 contractions per minute, p <0.05). This inhibition persisted a mean of 289.08 ± 91.24 seconds after deflating the rectal balloon., Conclusions: The inhibitory rectovesical reflex elicited by noxious colorectal distension clearly occurred in an isovolumetric bladder model with a ligated urethra but only to a negligible extent in filling related voiding contractions. Our results suggest that the inhibitory rectovesical reflex, most likely at the level of the lumbosacral spinal cord, is the result of an additive noxious urethral and colonic afferent stimulus., (Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

There are well established pressure flow criteria and nomograms for urinary obstruction in men. The pressure flow criteria for female urinary obstruction are not well established due to differences in female voiding dynamics as compared to men. Typically, other information such as radiographic data and clinical symptoms are needed to facilitate the diagnosis. Detrusor underactivity remains a poorly studied clinical condition without definitive urodynamic diagnostic criteria. Modalities proposed for objective analysis of detrusor function such as power (watt) factor, linear passive urethral resistance relation and BCI nomogram were all developed to analyze male voiding dysfunction. Overall, further investigation is needed to establish acceptable urodynamic criteria for defining detrusor underactivity in women., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The feasibility of estimating urinary flow velocity from the decorrelation of radiofrequency (RF) signals was investigated in soft tissue-mimicking models of obstructed and unobstructed urethras. The decorrelation was studied in the near field, focal zone and far field of the ultrasound beam. Furthermore, the effect of beam width was investigated. The results of this study suggest that it is feasible to estimate flow velocity in models of the urethra by quantifying the decorrelation of RF ultrasound signals. The decorrelation slope increased more rapidly and more linearly with increasing velocity in the focal zone than in the near and far field. A preliminary example of an in vivo measurement in a healthy volunteer illustrated that this method has potential for clinical use in the future., (Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.)

Objective: To improve the model for establishment and evaluation of detrusor overactivity in female Wistar rats., Materials and Methods: We ligated the perineal urethra of female Wistar rats and then performed filling cystometry. The probability of detrusor overactivity, bladder capacity, peak voiding pressure and histological changes were investigated., Results: Detrusor overactivity ratio of the obstruction group was 32.4%. Bladder capacity increased from 0.273 ± 0.036 mL in control group to 0.89 ± 0.19 mL in detrusor overactivity group (P < 0.001), and peak voiding pressure increased from 45.9 ± 4.1 cm.H2O to 63.5 ± 17.4 cm.H2O (P = 0.007). For obstruction group, compared to no detrusor overactivity rats, detrusor overactivity rats had higher bladder capacity (0.89 ± 0.19 mL versus 0.43 ± 0.09 mL, P < 0.001) and higher peak voiding pressure (63.5 ± 17.4 cm.H2O versus 44.8 ± 6.2 cm.H2O, P = 0.005). Detrusor overactivity rats were classified according to peak voiding pressure (49.2 ± 4.2 cm.H2O versus 80.8 ± 7.1cm.H2O, P < 0.001). Moreover, bladder weight increased significantly in detrusor overactivity rats (P = 0.003, P = 0.028) and detrusor histological hypertrophy was observed., Conclusions: Ligating perineal urethra and filling cystometry with intra-urethral cannula approach is a simple and easily reproducible method to establish and evaluate the model of detrusor overactivity in rats.

Objective: To investigate epidemiologic data, clinical signs, results of urinalysis and causes of lower urinary tract disease in a German veterinary hospital population of cats and to determine if the demographic data, history, clinical signs and urinalysis results correlate with a particular etiology., Materials and Methods: Cats presented with signs of feline lower urinary tract disease (FLUTD) with a documented history and physical examination, a complete urinalysis (urine specific gravity, urine dipstick and sediment, urine culture) of urine obtained by cystocentesis or catheterization, and diagnostic imaging of the urinary tract were included into the study. Cats that had received a previous treatment during the same episode of FLUTD were excluded., Results: A total of 302 cats were included into the study. Cats with FLUTD presented throughout the seasons with similar frequency. The most common diagnosis was feline idiopathic cystitis (FIC) (55.0%), followed by bacterial urinary tract infection (UTI) (18.9%), urethral plug (10.3%) and urolithiasis (7.0%). Urethral obstruction was significantly more frequent in cats with FIC than in cats with UTI. Cats with FIC and urethral plugs were significantly younger and had significantly higher body weights than cats with UTI and neoplasia. FIC and urethral plugs were significantly more common causes of FLUTD in cats younger than 10 years compared to cats that were 10 years or older (65.2% versus [vs.] 35.8% and 13.3% vs. 3.0%), while the incidences of UTI and neoplasia increased with age (12.9% vs. 41.8% and 1.0% vs. 13.4%)., Conclusion and Clinical Relevance: FIC and UTI are the most common diagnoses in cats with FLUTD, with a significant age-related difference in incidence.

Introduction and Hypothesis: The purpose of this study was to evaluate the predictors of de novo stress urinary incontinence (SUI) in patients undergoing a tension-free vaginal mesh procedure (TVM) for pelvic organ prolapse (POP)., Methods: Sixty-five patients without SUI were assessed with regard to voiding function by a pressure flow study and clinical characteristics., Results: The mean age of the patients was 67 ± 8.3. Of the 65 patients, 41 (63 %) maintained urinary continence postoperatively and 24 (37 %) showed de novo SUI. In univariate analysis, the de novo SUI group included a significantly higher proportion of patients with preoperative obstruction, defined as moderate or greater obstruction according to the Blaivas nomogram (29 vs 7 %, P = 0.035). In multivariate analysis, urethral obstruction was an independent predictor of de novo SUI with an odds ratio of 12.616 (95 % confidence interval 1.580-268.731)., Conclusions: Preoperative evaluation of urethral obstruction will contribute to prediction of de novo SUI combined with a conventional diagnosis of occult SUI.

Background: Microalbuminuria (MA) has been shown to be an early biomarker of renal damage. It is postulated that MA is the early result of hyperfiltration, which could evolve into glomerular sclerosis and renal failure if hyperfiltration is left untreated. We hypothesized that MA is a good indicator of hyperfiltration in children with kidney disorders, obviating the need to calculate the filtration fraction (FF)., Methods: A total of 155 children or young adults were prospectively included [42 single kidney (SK), 61 vesico-ureteral reflux, 23 obstructive uropathies, 29 other kidney diseases]. We measured inulin, para-aminohippuric acid clearances, FF and MA. Prediction of hyperfiltration was explored by studying the association between the FF and other variables such as urinary albumin (Alb), urinary albumin-creatinine ratio (ACR) and creatinine clearance., Results: A significant but weak association between urinary Alb or ACR and FF was found in subjects with an SK (Spearman correlation coefficients 0.32 and 0.19, respectively). Multivariate analysis also showed that urinary Alb and ACR significantly predict FF only in subjects with an SK (r(2) = 0.17, P = 0.01 and r(2) = 0.13, P = 0.02, respectively). This holds true only in subjects with an SK and inulin clearance >90 mL/min/1.73 m(2) (r(2) = 0.41, P < 0.001). There was no association between creatinine clearance and FF., Conclusions: MA is not associated with FF in our subjects with nephro-urological disorders, except in those with an SK, where the association is weak, indicating that MA is due to other mechanisms than high FF and cannot predict hyperfiltration in such groups.

Objectives: To examine the effect of partial urethral obstruction (PUO) on bladder smooth muscle outward potassium current and the contribution of the large-conductance calcium-activated potassium (Maxi-K, BKCa) channel to this activity in smooth muscle cells isolated from bladders of sham-operated and PUO male rats using whole-cell patch clamp recording techniques. To determine the effect of PUO on the expression of the Maxi-K channel α and β1 subunits and in vitro detrusor contractility., Materials and Methods: Twenty adult male Sprague-Dawley rats were divided equally into two groups and subjected to surgical ligation of the urethra (PUO) or sham surgery (SHAM). After 2 weeks, the detrusors from PUO and SHAM rats were used for molecular analyses (mRNA and protein quantification of Maxi-K subunits) or organ bath contractility studies, or myocytes were isolated for conventional whole-cell patch clamp analyses., Results: PUO increased bladder mass 2.5-fold and detrusor strips exhibited a more tonic-type contraction and increased contractility compared with controls (SHAM). Iberiotoxin (300 nM) sensitive Maxi-K channel current comprised about 40% of the outward whole-cell current in SHAM bladders but only about 8% in PUO bladders. Expression of the α subunit of the Maxi-K channel was significantly decreased ~40% while the expression of the β1 subunit was increased ~2-fold at the mRNA level. The increase in β1 expression was confirmed by Western blotting., Conclusions: Our findings show that obstruction of the rat bladder is associated with decreased Maxi-K channel activity of bladder smooth muscle cells, determined via direct current measurement. Increased expression of the β1 subunit points to a compensatory reaction to decreased Maxi-K channel activity. Maxi-K channel openers or gene therapy may therefore provide therapeutic benefit for the overactive bladder., (© 2012 BJU INTERNATIONAL.)

Background and Objectives: Obstructive nephropathy is a leading cause of CKD in children. The assessment of severity of renal impairment and the prediction of which children will progress to renal failure are, however, challenging., Design, Setting, Participants, & Measurements: This case-control study measured the urinary excretion of candidate biomarkers in 27 prevalent case-patients with posterior urethral valves (PUVs) and 20 age-matched controls, correlated their urinary concentration with GFR, and analyzed receiver-operating characteristic (ROC) curve and regression analyses to assess their performance as tests for low GFR., Results: The median urinary protein-to-creatinine ratio was higher in children with PUV (45 g/mol; range, 5-361 g/mol) than in controls (7 g/mol; range, 3-43 g/mol) (P<0.01) and correlated inversely with renal function (r = -0.44; P<0.05). In whole urine, excretion of aquaporin-2 was significantly decreased, whereas that of TGFβ and L1 cell adhesion molecule (L1CAM) was significantly increased. Whole-urine TGFβ excretion correlated inversely with GFR (r = -0.53; P<0.05). As tests for low GFR, whole-urine TGFβ, L1CAM, and urinary protein-to-creatinine ratio performed best, with areas under the ROC curves of 0.788, 0.795, and 0.814, respectively. By linear regression analysis, whole-urine TGFβ, L1CAM, and urinary protein-to-creatinine ratio were associated with low GFR in the case-patients., Conclusions: Candidate biomarkers of obstructive nephropathy can be readily measured in whole urine and in urine exosomes. In boys with PUV, these biomarkers correlate with GFR.

Objective: To compare the sex specific outcome of fetuses with prenatally detected urinary tract dilatation, with the exclusion of pyelectasia., Method: Included in the study were 709 cases of major dilatation of the fetal urinary tract, diagnosed at routine ultrasound scan. For each sex group, cases were divided into two subgroups depending on the level of dilatation. Final diagnosis was based on postnatal evaluation or on fetal autopsy. Postnatal renal function was evaluated using serum creatinine at two years of age., Results: Bilateral higher urinary tract dilatation was prenatally observed in 148 (20.8%) and lower urinary tract obstruction or bladder dilatation in 561 (79.1%) of the 709 cases (121 female and 588 male fetuses) (P <0.001). Bladder dilatation was less frequent in female fetuses (62%) than in males (82.6%) (P <0.001). At final diagnosis, associated malformations were observed in 53.7% of female fetuses versus 11% in males (P <0.001). The survival rate was 42.7%. Postnatal renal function, evaluated in 289/303 live infants, was impaired in 29.7% of cases and depended on the level of obstruction, but not on the sex., Conclusion: Prenatally detected urinary tract dilatation has a poor prognosis both in male and female fetuses. Associated malformations are observed more frequently in female than in male fetuses., (© 2012 John Wiley & Sons, Ltd.)

Introduction: Dilation of urinary tract occurs without the presence of obstruction. Diagnostic methods that depend on renal function may elicit mistaken diagnosis. Whitaker (1973) proposed the evaluation of urinary tract pressure submitted to constant flow. Other investigators proposed perfusion of renal pelvis under controlled pressure, making the method more physiological and reproducible. The objective of the present study was to evaluate the results of the anterograde pressure measurement (APM) of the urinary tract of children with persistent hydronephrosis after surgery suspected to present persistent obstruction., Materials and Methods: Along 12 years, 26 renal units with persistent hydronephrosis after surgery (12 PUJ and 14 VUJ) were submitted to evaluation of the renal tract pressure in order to decide the form of treatment. Previous radionuclide scans with DTPA, intravenous pyelographies and ultrasounds were considered undetermined in relation to obstruction in 10 occasions and obstructive in 16. APM was performed under radioscopy through renal pelvis puncture or previous stoma. Saline with methylene blue + iodine contrast was infused under constant pressure of 40 cm H2O to fill the urinary system. The ureteral opening pressure was measured following the opening of the system and stabilization of the water column., Results: Among the 10 cases with undetermined previous diagnosis, APM was considered non-obstructive in two and those were treated clinically and eight were considered obstructive and were submitted to surgery. Among the 16 cases previously classified as obstructive, nine confirmed obstruction and were submitted to surgery. Seven cases were considered non-obstructive, and were treated clinically, with stable DMSA and hydronephrosis., Conclusions: APM avoided unnecessary surgery in one third of the cases and was important to treatment decision in 100 %. We believe that this simple test is an excellent diagnostic tool when selectively applied mainly in the presence of functional deficit.

In animal models of partial urethral obstruction (PUO), altered smooth muscle function/contractility may be linked to changes in molecules that regulate calcium signaling/sensitization. PUO was created in male rats, and urodynamic studies were conducted 2 and 6 wk post-PUO. Cystometric recordings were analyzed for the presence or absence of nonvoiding contractions [i.e., detrusor overactivity (DO)]. RT-PCR and Western blots were performed on a subpopulation of rats to study the relationship between the expression of RhoA, L-type Ca(2+) channels, Rho kinase-1, Rho kinase-2, inositol 1,4,5-trisphosphate, ryanodine receptor, sarco(endo)plasmic reticulum Ca(2+)-ATPase 2 and protein kinase C (PKC)-potentiated phosphatase inhibitor of 17 kDa, and urodynamic findings in the same animal. Animals displayed DO at 2 (38%) and 6 wk (43%) post-PUO, increases were seen in in vivo pressures at 2 wk, and residual volume at 6 wk. Statistical analysis of RT-PCR and Western blot data at 2 wk, during the compensatory phase of detrusor hypertrophy, documented that expression of molecules that regulate calcium signaling and sensitization was consistently lower in obstructed rats without DO than those with DO or control rats. Among rats with DO at 2 wk, linear regression analysis revealed positive correlations between in vivo pressures and protein and mRNA expression of several regulatory molecules. At 6 wk, in the presence of overt signs of bladder decompensation, no clear or consistent alterations in expression of these same targets were observed at the protein level. These data extend prior work to suggest that molecular profiling of key regulatory molecules during the progression of PUO-mediated bladder dysfunction may shed new light on potential biomarkers and/or therapeutic targets.

Introduction and Hypothesis: Iatrogenic female urethral obstruction resulting from sling operations may be related to surgical inexperience and must be better understood. Although there are no widely recognized parameters for this type of study, a single-surgeon consecutive series offers an opportunity to study the role of expertise in sling operations over time., Methods: This study consecutively examined 176 women who underwent an autologous fascial sling procedure. Postoperative urethral obstruction was identified by the occurrence of voiding dysfunctions. Clinically obstructed patients were invited to undergo a postoperative urodynamic evaluation after 3 months. To enable comparison, patients were placed into 6-month groups according to the time of surgery., Results: A total of 159 cases were evaluated with a mean follow-up time of 32.4 ± 13.4 months. Stress continence was cured in 97.5% of cases. Although 29 patients were identified as obstructed, only 20 underwent a postoperative urodynamic evaluation. Only five of the clinically obstructed cases showed a high P(det)Q(max). All of the other cases met one or more of the non-classic parameters linked to obstruction. Overactive bladder was present in 14 (63.6%) of the obstructed cases. Iatrogenic urethral obstruction was more common among the early cases (30.4%) than among the later ones (5%) (P < 0.001). Postoperative urodynamic evaluation showed a trend toward obstruction on pressure flow studies., Conclusions: Autologous fascial sling operations require expertise and involve a clear surgical learning curve. Iatrogenic obstruction in females does not fit a single model and may be difficult to recognize. Obstruction in females must be identified through clinical indicators and postoperative urinary complaints rather than the high detrusor pressure observed in men. Furthermore, iatrogenic female obstruction can probably be minimized but not eliminated.

Introduction and Hypothesis: We compared pre- and postoperative voiding function in patients with POP and assessed the efficacy of urodynamic studies in these cases., Methods: Forty-six patients treated with the tension-free vaginal mesh (TVM) procedure between January 2009 and February 2010 underwent pressure flow study pre- and postoperatively. Pre- and postoperative voiding functions were assessed according to Schäfer nomograms., Results: The mean postoperative detrusor pressure at maximal flow was decreased significantly compared with that preoperatively. The mean maximum flow rate was also improved significantly and the proportion of normal contractility was increased significantly after the operation, as was the proportion of non-obstructive patients., Conclusions: The TVM procedure for pelvic organ prolapse improved both detrusor contractility and urethral obstruction.

Aims: Beta3-adrenoceptor selective agonists are evaluated as a new treatment for patients with lower urinary tract symptoms . It is believed that β3-AR selective agonists exert their effects via a peripheral site of action. However, β3-ARs have been found in brain tissue. This study examined whether β3-ARs are present in rat sacral spinal cord, and whether there are differences in β3-AR expression between normal and partial urethral obstruction (PUO) animals, and furthermore assessed the functional relevance of spinal β3-ARs for micturition., Methods: Thirty-eight male Sprague-Dawley rats underwent either PUO or sham-operation. Two weeks after operation, half of the animals were used for histomorphological analysis. Remaining animals were used for functional experiments, where a β3-AR selective agonist, BRL 37344, was given intrathecally. Bladder function was assessed by continuous cystometry in non-anesthetized animals before and after drug administration., Results: Beta3-ARs were found in sacral spinal cord segments with an accumulation in the ventral horn. There was a significant increase of β3-AR expression in obstructed rats. In functional experiments obstructed rats showed increased bladder weight, micturition frequency, spontaneous activity, and bladder pressures (all P < 0.05) compared to controls. Intrathecally administered BRL 37344 showed no effect in non-obstructed rats. In obstructed rats intrathecal BRL 37344 significantly reduced bladder pressures, spontaneous activity, and micturition frequency (all P < 0.05)., Conclusions: Beta3-ARs are present in rat sacral spinal cord, and are significantly up-regulated after PUO. Besides their well-established peripheral site of action in the treatment of voiding dysfunction, β3-AR selective agonists might exert relevant effects at a central nervous site of action., (Copyright © 2011 Wiley-Liss, Inc.)

Aim: Obstructive uropathies (OU) in childhood constitute one of the major causes of chronic renal insufficiency. Transforming growth factor-β1 (TGF-β1) is considered to be the major fibrogenic growth factor. The aim of the present study was to investigate urinary TGF-β1 levels in children with obstructive and non-obstructive uropathies (NOU)., Methods: This study involved 19 children with OU, 11 children with non-obstructive hydronephrosis and 21 healthy children. Urinary TGF-β1, proteinuria, microalbuminuria and urinary α1-microglobulin were measured, and renal function was assessed. The results were statistically analyzed., Results: Mean urinary TGF-β1 concentrations in patients with OU were significantly higher than those with NOU (4.14 ± 0.67 creatinine vs 1.80 ± 0.24 pg/mmol creatinine, P < 0.05) and healthy controls (1.66 ± 0.28 pg/mmol creatinine, P < 0.05). Positive correlations of urinary TGF-β1 concentrations with proteinuria (r = 0.87, P < 0.0001) and urinary α1-microglobulin (r = 0.82, P = 0.0002) were found in patients with OU., Conclusion: Children with OU have higher urinary TGF-β1 than children with NOU. Urinary TGF-β1 may be a useful non-invasive tool for the differential diagnosis between OU and NOU in children. A positive correlation of TGF-β1 with markers of renal tissue damage in patients with OU was found., (© 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology.)

Unlabelled: Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? We have clarified that there exist two types of voiding urodynamics (pressure-flow-study) for congenital urethral obstruction in boys; one is synergic pattern (SP) and the other is dyssynergic pattern (DP). In terms of daytime incontinence and nocturnal enuresis, the transurethral endoscopic incision of these obstructive lesions is only effective in the SP type, while never effective in the DP type. The synergic pattern (SP) seems to represent simple anatomical obstruction, while the dyssynergic pattern (DP) may represent anatomical obstruction complicated with functional obstruction. The efficacy of endoscopic incision to mild forms of congenital urethral obstruction has been controversial, especially in terms of nocturnal enuresis. One of the reasons for the controversy is due to the lack of pre-and post-operative urodynamic assessment with its linkage to symptomatic change. We have, for the first time in the world, systematically conducted voiding urodynamic study for those elusive lesions seen in enuretic boys. Conclusively, for simple mechanical obstruction (SP), we confirmed that some voiding urodynamic parameters improve after the endoscopic incision, parallel to symptomatic improvement, while in the rest (DP) endoscopic incision is never effective. The cause of this ineffectiveness seemed to be due to persistent functional obstruction having superimposed on mechanical obstruction. The result of the study urges us to be more keen to diagnose and treat the mild congenial urethral obstruction as well as the concomitant functional obstruction in boys with nocturnal enuresis., Objective: • To evaluate the clinical significance of congenital obstructive lesions of the posterior urethra in boys with refractory primary nocturnal enuresis., Patients and Methods: • VCUG was performed in 43 consecutive boys who visited our department from April 2004 to April 2009 who were unresponsive to conservative treatment. 20 patients of the 43 patients, underwent TUI. VCUG and UDS were performed before and 3-4 months after TUI. • In UDS, the maximum flow rate (Qmax), maximum bladder capacity, and post-voiding residual urine volume were determined using uroflowmetry (UFM), and the detrusor pressure (Pdet) at Qmax was determined in a pressure flow study (PFS). • Clinical outcome was evaluated 3-4 months and 6 months after TUI., Results: • In VCUG performed 3-4 months after TUI, improvement was observed in urethral morphology in all patients. In preoperative PFS, two patterns were observed: 13 patients (65%) had a synergic pattern (SP) in which the Pdet increased with increasing urinary flow rate simultaneously with the initiation of voiding and seven (35%) had a dyssynergic pattern (DP) in which the Pdet was not coincident with the initiation of voiding, but was higher immediately before voiding than at Qmax. TUI was effective only in the SP group: symptomatic improvement was observed in 87.5% of patients with daytime incontinence and 77% of patients with nocturnal enuresis 6 months after TUI. • In the DP group, no effect was observed (0%). With regard to changes in UDS parameters, a significant decrease (P= 0.0004) was observed in the Pdet at Qmax and a significant increase (P= 0.036) was observed in the maximum bladder capacity in the SP group, whereas no significant differences were noted in any parameters in the DP group., Conclusion: • Two voiding urodynamic patterns with different clinical outcomes of TUI were detected among patients with congenital posterior urethral obstruction, the underlying disease of refractory primary nocturnal enuresis in boys.

Purpose: The aim of the study was to report the surgical complications that may occur during or after primary ablation of posterior urethral valve (PUV) in a large number of cases treated using different modalities., Materials and Methods: We retrospectively reviewed a database of 291 patients with PUV treated by primary valve ablation from 2 separate centers between 1987 and 2006. Primary valve ablation was performed in all patients regardless of serum creatinine level or upper tract configuration. A hot loop resectoscope was used in 122 patients, cold knife urethrotome in 108, a hook diathermy electrode in 18, a diathermy coagulation bugbee electrode in 20, whereas stripping using a Fogarty catheter was performed in 23., Results: The follow-up duration ranged from 1.5 to 20 years (median, 6.5). Early postoperative complications occurred in 22 patients (7.5%). The most common complication was urinary retention in 16 patients (5.5%). Urinary extravasations occurred in 3 cases, significant hematuria from urethral bleeding occurred in 2, and obstructive anuria developed in 1 patient. Most of cases were treated conservatively. Urethral strictures developed in 6 patients (2%) mainly after endoscopic loop resection (4/6). All were treated by visual internal urethrotomy and urethral dilatation with successful results without the need of open urethroplasty., Conclusions: Primary valve ablation seems to be safe and is associated with low rate of postoperative complications. All the complications could be treated conservatively. Urethral stricture may occur after valve ablation in a minority of cases and can be successfully treated endoscopically. Loop resection is associated with more strictures., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objective: To compare the renal and cardiorespiratory effects of IV treatment with lactated Ringer's solution (LRS) or physiologic saline (0.9% NaCl) solution (PSS) in severely decompensated cats with urethral obstruction (UO)., Animals: 14 cats (4 cats were used only to establish infusion rates)., Procedures: An occluded urethral catheter was used to induce UO in each cat. After development of severe metabolic acidosis, hyperkalemia, and postrenal azotemia, the obstruction was relieved (0 hours); LRS or PSS (5 cats/group) was administered IV (gradually decreasing rate) beginning 15 minutes before and continuing for 48 hours after UO relief. Ten minutes before urethral catheter placement (baseline), at start of fluid therapy (SFT), and at intervals during fluid administration, various physical and clinicopathologic evaluations were performed., Results: Metabolic acidosis was detected in the PSS-treated group at SFT and 2 hours after relief of UO and in the LRS-treated group only at SFT The PSS-treated group had significantly lower blood pH and bicarbonate concentrations at 8 through 48 hours and lower base excess values at 2 through 48 hours, compared with the LRS-treated group. Hypocalcemia and hypernatremia were detected in the PSS-treated group at 2 and 12 hours, respectively. Absolute serum potassium and chloride concentrations did not differ significantly between groups at any time point., Conclusions and Clinical Relevance: Treatment with LRS or PSS appeared to be safe and effective in cats with experimentally induced UO; however, LRS was more efficient in restoring the acid-base and electrolyte balance in severely decompensated cats with UO.

Objective: To evaluate the urodynamic effects of fesoterodine, a new antimuscarinic agent, alone and combined with doxazosin, in a rat model of partial urethral obstruction (PUO), as 35-83% of men with bladder outlet obstruction (BOO) secondary to benign prostatic hyperplasia (BPH) have overactive bladder (OAB) syndrome, and as the combination of alpha(1)-adrenoceptor- and muscarinic-receptor antagonists has been proposed to be beneficial for these patients., Materials and Methods: Thirty-seven male Sprague-Dawley rats (250 g) had surgically induced PUO; 2 weeks later they were evaluated by cystometry with no anaesthesia or any restraint. After a 1-h period either 5-hydroxymethyl tolterodine (5-HMT, the active metabolite of fesoterodine, previously known as SPM 7605), doxazosin or a combination of both, was given intravenously (0.1 mg/kg body weight), and cystometry was continued for another 45 min. Fifteen healthy, age-matched rats served as a control., Results: At 2 weeks after surgery the obstructed rats had an greater bladder weight, threshold pressure (TP) and micturition frequency (MF), and lower bladder capacity (BCap) and micturition volume (MV) than the controls. 5-HMT did not cause urinary retention in obstructed rats, but decreased TP, maximum pressure (MP), spontaneous bladder activity (SA) and, paradoxically, increased MF. Doxazosin alone decreased TP, MP, MF and increased BCap and MV. 5-HMT and doxazosin together did not depress the ability to empty the bladder, and showed decreased TP, MP and SA., Conclusions: 5-HMT, alone and in combination, did not impair the voiding ability in obstructed rats. Doxazosin counteracted some of the 'negative' effects of 5-HMT in this model (increase of MF) and did not attenuate the 'positive' effects (decrease of bladder SA). In this model, the combination of 5-HMT and doxazosin appeared to be urodynamically safe and well tolerated.

Introduction: Posterior urethral valve (PUV) is a congenital obstructive defect of the male urethra with an incidence of 1/8,000 to 1/25,000 live births. PUV is the most common cause of lower urinary tract obstruction in neonates. The diagnosis of PUV is usually made early, and PUV cases have rarely been detected in adults., Case Presentation: Here we report the case of a 35 years old man presented with obstructive urinary symptoms. In spite of bladder neck rejection uroflowmetry pointed out infravesical obstruction with max. flow rate 9 ml/s and average flow rate 6 ml/s in uroflowmetry. During cystoscopy mild bladder trabeculation and resected bladder neck were seen. While the cystoscope was taken off, PUV were obtained., Conclusion: Since PUV is a rare condition in adults and the diagnosis of PUVs is also difficult in these groups we must consider this situation during evaluation of adult patients with obstructive symptoms especially during cystourethroscopy.

Objective: To study the effects of the phosphodiesterase-5 inhibitor, vardenafil, on contraction and cyclic nucleotide levels in isolated detrusor preparations with and without mucosa, from control rats and rats with partial urethral obstruction (PUO) and intact mucosa., Materials and Methods: Female Sprague-Dawley rats were divided into groups subjected to PUO for 14 days (six), and sham-operated control rats (12). Detrusor preparations were mounted in organ baths and effects of increasing concentrations of vardenafil (1 nm to 100 microm) assessed on carbachol-activated (1 microm) preparations, and on contractions induced by transmural activation of nerves (electrical field stimulation, EFS). Levels of cGMP and cAMP were determined using radioimmunoassays., Results: Vardenafil caused concentration-dependent relaxations of carbachol-contracted detrusor, the mean (sd) of which at 100 microm was 91 (4)% in control and 100% in PUO rats. The -log 50% inhibitory concentration (IC(50)) was 4.41 (0.08) and 4.73 (0.05) (P < 0.01), respectively. Removing the mucosa increased the relaxant effect of vardenafil at 1-10 microm (P < 0.05) although -log IC(50) values were unaffected compared to the control. The cGMP levels ( pmol/mg protein) in control preparations increased from 2.5 (0.6) to 5.0 (0.8), and from 1.4 (0.2) to 7.2 (1.3) in obstructed bladders. In mucosa-denuded preparations the cGMP content increased from 0.6 (0.1) to 1.6 (0.4) in response to vardenafil. In control rats, the levels of cAMP increased from 12.8 (2.5) to 18.9 (0.9) (P < 0.05) after vardenafil. In mucosa-denuded preparations the cAMP levels after vardenafil increased from 16.5 (2.11) to 37.8 (3.4) (P < 0.01). In PUO bladders, the tissue content of cAMP increased from 12.6 (2.4) to 20.6 (3.4) (P < 0.01). Vardenafil concentration-dependently inhibited nerve-induced contractions in all groups studied. At 100 microm 19 (3)% of the control contraction remained, vs 8 (1)% for preparations from obstructed rats, and 11 (4)% in mucosa-denuded preparations., Conclusion: In normal rats, vardenafil relaxed carbachol- and inhibited EFS-induced contractions of detrusor preparations with and without urothelium, and in PUO rats with urothelium. Relaxations were accompanied by increases in both cAMP and cGMP content. It is proposed that vardenafil-induced relaxation of rat detrusor, also in obstructed and mucosa-denuded preparations, is mediated via cAMP.

Obstructive uropathy can cause irreversible renal damage. It has been hypothesized that elevated hydrostatic pressure within renal tubules and/or renal ischemia contributes to cellular injury following obstruction. However, these assaults are essentially impossible to isolate in vivo. Therefore, we developed a novel pressure system to evaluate the isolated and coordinated effects of elevated hydrostatic pressure and ischemic insults on renal cells in vitro. Cells were subjected to: (1) elevated hydrostatic pressure (80 cm H(2)O); (2) ischemic insults (hypoxia (0% O(2)), hypercapnia (20% CO(2)), and 0 mM glucose media); and (3) elevated pressure + ischemic insults. Cellular responses including cell density, lactate dehydrogenase (LDH) release, and intracellular LDH (LDH(i)), were recorded after 24 h of insult and following recovery. Data were analyzed to assess the primary effects of ischemic insults and elevated pressure. Unlike pressure, ischemic insults exerted a primary effect on nearly all response measurements. We also evaluated the data for insult interactions and identified significant interactions between ischemic insults and pressure. Altogether, findings indicate that pressure may sub-lethally effect cells and alter cellular metabolism (LDH(i)) and membrane properties. Results suggest that renal ischemia may be the primary, but not the sole, cause of cellular injury induced by obstructive uropathy.

The afferent innervation of the urinary bladder consists primarily of small myelinated (Adelta) and unmyelinated (C-fiber) axons that respond to chemical and mechanical stimuli. Immunochemical studies indicate that bladder afferent neurons synthesize several putative neurotransmitters, including neuropeptides, glutamic acid, aspartic acid, and nitric oxide. The afferent neurons also express various types of receptors and ion channels, including transient receptor potential channels, purinergic, muscarinic, endothelin, neurotrophic factor, and estrogen receptors. Patch-clamp recordings in dissociated bladder afferent neurons and recordings of bladder afferent nerve activity have revealed that activation of many of these receptors enhances neuronal excitability. Afferent nerves can respond to chemicals present in urine as well as chemicals released in the bladder wall from nerves, smooth muscle, inflammatory cells, and epithelial cells lining the bladder lumen. Pathological conditions alter the chemical and electrical properties of bladder afferent pathways, leading to urinary urgency, increased voiding frequency, nocturia, urinary incontinence, and pain. Neurotrophic factors have been implicated in the pathophysiological mechanisms underlying the sensitization of bladder afferent nerves. Neurotoxins such as capsaicin, resiniferatoxin, and botulinum neurotoxin that target sensory nerves are useful in treating disorders of the lower urinary tract.

Role of the intermediate filament protein desmin in hypertrophy of smooth muscle was examined in desmin-deficient mice (Des(-/-)). A partial obstruction of the urethra was created, and after 9-19 days bladder weight increased approximately threefold in both Des(-/-) and wild type (Des(+/+)) animals. Bladder growth was associated with the synthesis of actin and myosin. In the hypertrophic Des(+/+) bladder, the relative content of desmin increased. In Des(-/-)mice, desmin was absent. No alterations in the amount of vimentin were observed. Although Des(-/-) obstructed bladders were capable of growth, they had structural changes with a partial disruption of the wall. Des(-/-)bladders had slightly lower passive stress and significantly lower active stress compared with Des(+/+). Des(-/-)preparations had lower shortening velocity. During hypertrophy, these structural and mechanical alterations in the Des(-/-)urinary bladder became more pronounced. In conclusion, desmin in the bladder smooth muscle is not needed for growth but has a role in active force transmission and maintenance of wall structure.

Posterior urethral valve (PUV) obstruction is the most common cause of bladder outlet obstruction in boys. Currently, the diagnosis of PUV is commonly made prenatally. In our environment, however, prenatal diagnosis is rare and the diagnosis is usually made postnatally from the clinical and radiological features. This study therefore examines the clinical and radiological spectrum of boys with PUV in our environment. We examined the clinical presentations, ultrasonographic and the micturating cystourethrographic (MCUG) features of boys with PUV in our institution over a 22-month period from June 2006. There were 28 patients with PUV over this period. The age at presentation ranged from 11 days to 11 years (mean age = 2.7 years). Although prenatal ultrasound scan was done in 23 (82.1%) patients, no prenatal diagnosis was made in any of the patients. The diagnosis was made after infancy in 16 (57.1%) patients. Recurrent urinary tract infection (UTI) was the most common mode of presentation occurring in 14 (50.0%) patients with 7 (50.0%) of the patients with UTI presenting with septicaemia. Voiding dysfunctions, which occurred in all the patients, were the primary mode of presentation in 12 (42.9%) patients. Three (10.7%) patients presented with renal insufficiency, which was significantly associated with the age at presentation (P = 0.026). Ultrasound scan done in the postnatal period strongly suggested the diagnosis of posterior urethral valves in 22 (78.6%) patients in whom the posterior urethra was found to be dilated, associated with thick-walled urinary bladder and bilateral hydronephrosis. Trabeculations of the bladder was a constant feature on MCUG. Other features on MCUG included dilatation of the posterior urethra in 26 (92.8%), bladder diverticuli in 15 (53.6%) and unilateral and bilateral vesicoureteric reflux in 3 (10.7%) and 1 (3.6%) patient(s), respectively. The diagnosis of PUV obstruction which is often made late in our environment, is mainly by clinical, sonographic and MCUG features in the postnatal period. A majority of patients present late, with recurrent UTI.