The Release of 24 h Infravesical Obstruction in Mice: Changes in Molecular, Morphological, and Functional Parameters for 14-Day Observation.

Bladder outlet obstruction (BOO) induces bladder dysfunction and altered bladder architecture. Irrespective of the release of the obstruction, persistent bladder dysfunction severely affects the quality of life. A better understanding of the repair process offers an opportunity to enhance postintervention management. We subsequently evaluated the postobstructive repair process in mice subjected to 24 h BOO followed by release. Male and female mice bladders were obstructed for 24 h by placing a clip around the bladder neck. After the release of obstruction, the mice were studied for 3, 7, and 14 days to observe the bladder repair process over time. Voiding frequency and volume were recorded using the voiding spot assay, and the transcutaneous glomerular filtration rate (tGFR) was measured. Fibrogenesis and associated gene expressions and altered protein levels were evaluated in the bladder using histology, quantatative polymerase chain reaction (qPCR), and Western blot analyses. Bladder wall thickness was increased in both genders over time but occurred later in female mice. Moreover, collagen deposition in the smooth muscle layer increased over time in both genders. Male mice showed a decreased average voided volume at 3 days post release, while female mice showed no significant change during the time course. Fibrosis-related molecular events, including upregulation of fibronectin (FN) protein and Collagen-3 (Col-3) mRNA expression, were transient and normalized again at 14 days in both genders. Transforming growth factor-ß (TGF-ß) and bone morphogenic protein (BMP)-7 mRNA expressions were upregulated at 14 days post release in both genders. Transcutaneous GFR remained normal during the time course. Release of 24 h BOO initiated a bladder remodeling process. The animal model enables a wide range of experiments to study bladder remodeling, and gender differences offer potential targets for understanding bladder fibrosis and adaptation with BOO.

Gender-dependent bladder response to one-day bladder outlet obstruction.

BACKGROUND: Development of bladder fibrosis, loss of compliance, and voiding dysfunction are among the severe consequences of various lower urinary conditions, for example, bladder outlet obstruction (BOO), neurogenic bladder, and radiotherapy to the pelvic area. The bladder remodelling results in significant changes in bladder function and architecture, and may ultimately be deleterious for kidney function. The molecular signals underlying pathologic bladder remodelling, as well as the impact of gender, remain poorly understood. OBJECTIVE: To investigate the bladder remodelling after one day BOO, whether the remodelling is different between different bladder sections, and whether genders may affect the remodelling. STUDY DESIGN: Thirty male and 30 female C57BL/6NRj mice were randomly divided into Control, Sham and BOO groups with ten mice per group. A 24-h total urethral obstruction was performed at the proximal urethra. Histological changes were observed via H&E, trichrome and immunohistochemistry staining. Harvested bladders were divided into upper and lower sections for analysis. Protein and gene expression were detected by Western blotting and qPCR. RESULTS: No significant changes in bladder wall thickness were observed following BOO, while increased bladder mass after BOO was found in female mice only. We detected FN and ⍺-SMA upregulation in the male upper bladder segment. Female BOO mice bladders showed increased α-SMA expression in both bladder segments, but no difference of FN was observed in either bladder segments. BOO-induced upregulation of TGF-ß and Gremlin were detected in both male and female bladders, while downregulation of BMP-7 was detected only in male bladders. Furthermore, phosphorylation of both SMAD2/3 and SMAD1/5/9 were increased in male bladders following BOO, whereas female mice exhibited increased pSMAD2/3 in the upper and increased pSMAD1/5/9 in the lower bladder segment. CONCLUSIONS: Our data indicate that some specific proteins and growth factors were detected as early alterations of tissue which may lead to fibrosis. In addition, the males tended to have more pronounced response than females. However, the causes and consequences of the findings need to be further investigated.

Accuracy of the hypospadias diagnoses and surgical treatment registrations in the Danish National Patient Register.

PURPOSE: The Danish National Health registers provide a valuable data source that offers unique opportunities for observational research, including studies on the congenital anomaly hypospadias. The accuracy of the diagnosis and surgical treatment registration of hypospadias in the Danish National Patient Register (DNPR) remains unknown. PATIENTS AND METHODS: We randomly sampled 500 patients diagnosed with hypospadias in the DNPR from January 1, 1995 to December 31, 2012. Among these, 384 patients were also registered with surgical treatment for hypospadias. Medical records were collected and reviewed independently by two investigators. Any classification disagreements were resolved by consensus. Using the medical records as the gold standard, we estimated positive predictive values (PPVs) with 95% confidence intervals (CIs) for the hypospadias diagnoses and surgical treatment registrations overall, as well as for the clinical subtypes. RESULTS: We were able to retrieve medical records for 463 (92.6%) patients with hypospadias diagnoses and for 329 (85.7%) patients registered with surgical treatment. Presence of hypospadias was confirmed in 450 of 463 patients, yielding an overall PPV (95% CI) of 97.6% (95.8%-98.7%). For subtypes of hypospadias, the PPVs ranged between 37.5% and 72.7%. For surgical treatment of hypospadias, the overall PPV was 99.7% (97.9%-99.9%). CONCLUSION: The validity of the registration of hypospadias diagnoses as well as surgical treatment for hypospadias in the DNPR is overall very high. For the specific subtypes of hypospadias diagnoses codes and the specific surgical treatment codes, the PPVs are lower and cautious use is warranted. However, the DNPR remains a valuable tool for future observational research on hypospadias.

Can bladder fibrosis in congenital urinary tract obstruction be reversed?

A variety of conditions exists in adults and children in which functional or anatomical urinary tract obstructions cause bladder fibrosis, which reduces the bladder's ability to store and empty urine. Current surgical procedures include removal of the obstructions to facilitate bladder emptying or prompt prenatal or postnatal spinal closure to prevent further neurogenic damage. Bladder fibrosis may occur, and it can get worse if a flow hindrance persists or deteriorates. Anti-fibrotic therapeutic strategies that target a variety of factors have been developed in animal models, but currently there are no anti-fibrotic therapies available for clinical use. This review examines the pathogenesis of bladder fibrosis that is caused by congenital obstructions of the lower urinary tract, and it focuses on the principal signalling factors and potential treatment modalities.

WITHDRAWN: Introductory editorial - Basic science.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.jpurol.2016.01.009. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.

Promising long-term outcome of bladder autoaugmentation in children with neurogenic bladder dysfunction.

PURPOSE: We evaluated the long-term outcome of bladder autoaugmentation in children with neurogenic bladder dysfunction. MATERIALS AND METHODS: Data were compiled from the records of 25 children with a median age of 9.3 years (range 0.9 to 14.2) who underwent detrusor myotomy between 1992 and 2008. All patients were diagnosed with small bladder capacity, low compliance and high end filling pressures, and were unresponsive to clean intermittent catheterization and anticholinergics. RESULTS: Median followup was 6.8 years (range 0.1 to 15.6). Median postoperative bladder capacity was unchanged or decreased to 95 ml (range 25 to 274) during the first 3 months compared to a median preoperative capacity of 103 ml (14 to 250). At 5 months postoperatively median bladder capacity increased significantly to 176 ml (range 70 to 420, p<0.01). This increase remained significant during the rest of followup. Median bladder compliance doubled after 1 year to 10 ml/cm H2O (range 1 to 31, p<0.05) compared to the preoperative level, and further increased to 17 ml/cm H2O (5 to 55) at 5 years (p<0.05). Median maximal detrusor pressure was 43 cm H2O (range 8 to 140) preoperatively. This value decreased significantly postoperatively (p<0.01) and at final followup it was 26 cm H2O (range 6 to 97). Kidney function developed normally in all patients except 1 with persistent uremia. Reflux was alleviated in 7 of 9 cases. Of the patients 18 became continent on clean intermittent catheterization. CONCLUSIONS: Bladder autoaugmentation in children with neurogenic bladder dysfunction offers, after a transient decrease in bladder capacity, a long lasting increase in capacity and compliance, while the end filling pressure decreases.

Urinary flow patterns in infants with distal hypospadias.

OBJECTIVE: To investigate preoperative urinary flow patterns in hypospadic infants and compare them to those from normal infant boys. PATIENTS AND METHODS: Twenty-one boys (median age 14.0, range 12.8-21.6 months) referred for distal hypospadias surgery were compared to 19 healthy boys (median age 12.0, 9.2-19.8 months). In both groups a 14-mm transit-time ultrasound flow probe mounted around the base of the penis continuously registered uroflow. RESULTS: Median maximum flow rate (Q(max)) was significantly lower in hypospadics (2.4 vs 4.4 ml/s, P < 0.01) while there was no difference in the voided volume per micturition (19.0 vs 21.0 ml, P 0.33). Flow curve pattern analysis revealed plateau-shaped curves in 31% of hypospadics compared to none in normal infant boys. Interestingly, dyscoordinated flow curves (interrupted, staccato, spike-dome) were less common in the hypospadics (36% vs 64%, P < 0.01). Meatal size did not correlate to Q(max) (rho = 0.26, P = 0.26). CONCLUSIONS: Infants with hypospadias void with a lower Q(max) and a lesser degree of dyscoordination as compared to normal infant boys. It can be speculated that decreased urethral compliance may contribute to the lower Q(max) and may act as a silencer for dyscoordination.

Microdialysis for detection of renal ischemia after experimental renal transplantation.

PURPOSE: We designed an experimental renal transplantation model and evaluated microdialysis as a detector of induced postoperative ischemia, a feared complication that when caused by vascular thrombosis most often causes renal graft loss. MATERIALS AND METHODS: Two microdialysis catheters were placed in the left kidney in 16 pigs, including 1 superficially in the renal cortex and 1 fixed on the renal capsule. Two-hour baseline measurements were made at steady state, after which the kidney was removed and subjected to warm and cold ischemia. It was subsequently re-anastomosed end to end in situ and reperfused for 5 hours. Pigs were then randomized into a total renal artery occlusion and a control group. RESULTS: At baseline there were no changes in local metabolites (glucose, glutamate, glycerol and lactate) and no significant difference between the groups. Glycerol increased 4-fold in each group during cold ischemia but there were no pivotal alterations in other metabolites. After kidney reperfusion glycerol decreased and all metabolites were in steady state after 1 hour. At 30 minutes after postoperative ischemia was introduced there were significant increases in all kidneys in ischemia vs steady state reperfusion levels of cortical lactate, glutamate, glycerol and the lactate-to-glucose ratio (each rank sum test p <0.001). No metabolic changes were seen in controls. CONCLUSIONS: Microdialysis detected significant metabolic changes after postoperative ischemia in pigs with experimental renal transplantation, while no metabolic changes were observed in controls. In the future microdialysis may become a valuable tool for postoperative observation of transplanted kidneys, most probably with major impact on early graft survival.

Early detection of renal ischemia by in situ microdialysis: an experimental study.

PURPOSE: Acute vascular thrombosis of the renal artery or vein is a feared and devastating complication after renal operations, especially transplantation. We evaluated microdialysis as a possible new tool for the rapid and reliable detection of renal ischemia in a porcine model. MATERIALS AND METHODS: A total of 20 healthy anesthetized pigs were randomized to experiments on the left or right kidney and into 3 groups, including arterial ischemia in 8, venous ischemia in 8 and 4 controls. One microdialysis catheter was inserted superficially in the renal cortex and 1 was placed outside on the renal capsule. The contralateral kidney was removed. After 2 hours of baseline measurements ischemia was introduced by clamping the renal artery or vein in the first 2 groups. Microdialysis samples were taken every 30 minutes during baseline and the following 5 hours. The samples were analyzed for glucose, lactate, glutamate and glycerol. The mean change from baseline was analyzed for each metabolite in all groups. RESULTS: At 30 minutes after the introduction of arterial or venous ischemia there was a significant increased mean change from baseline of glutamate, glycerol and lactate in the cortex and of glutamate extracapsularly. The mean change from baseline of glucose in the cortex decreased significantly 60 minutes after venous ischemia and 90 minutes after arterial ischemia. In controls these metabolites did not change significantly from baseline with time. CONCLUSIONS: Microdialysis from just outside the renal capsule is a reliable tool for the early detection of acute renal ischemia. It may be used to detect acute vascular complications in the first days after renal transplantation.