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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.)

Congenital obstructive nephropathy is the primary cause for end-stage renal disease (ESRD) in children. An increasingly used animal model of obstructive nephropathy is unilateral ureteral obstruction (UUO). This model mimics, in an accelerated manner, the different stages of obstructive nephropathy leading to tubulointerstitial fibrosis: cellular infiltration, tubular proliferation and apoptosis, epithelial-mesenchymal transition (EMT), (myo)fibroblast accumulation, increased extracellular matrix (ECM) deposition, and tubular atrophy. During the last decade genetically modified animals are increasingly used to study the development of obstructive nephropathy. Although the use of these animals (mainly knockouts) has highlighted some pitfalls of this approach (compensation by closely related gene products, absence of temporal knockouts) it has brought important information about the role of specific gene-products in the pathogenesis of obstructive nephropathy. Besides confirming the important pathologic role for angiotensin II (Ang II) and transforming growth factor-beta (TGF-beta) in obstructive nephropathy, these animals have shown the complexity of the development of tubulointerstitial fibrosis involving a large number of closely functionally related molecules. More interestingly, the use of these animals has led to the discovery of unexpected and contradictory roles (both potentially pro- and antifibrotic) for Ang II, for ECM degrading enzymes matrix metalloproteinase 9 (MMP-9) and tissue plasminogen activators (PAs), for plasminogen activator inhibitor 1 (PAI-1), and for the adhesion molecule osteopontin (OPN) in obstructive nephropathy. Further use of these animals, especially in combination with pharmacologic tools, should help to better identify potential antifibrotic strategies in obstructive nephropathy.

To assess urethral resistance and changes in the urethral elasticity during voiding, a lumped parameter model of the urethra was developed. The model uses pressure and flow measurements to estimate time-dependent resistance and elasticity factor. The model includes a resistance that has a function of the cross-section and urethral elasticity. Two resistivity types are compared in the constricted flow-controlling zone of the urethra: Poiseouille resistance and the Bernoulli effect. Using real pressure-flow data sets, the model was used to estimate urethral resistance and changes in urethral elasticity during voiding. Estimation of the elasticity show that in a normal patient relaxation of the urethra is a process that continues until the end of voiding. This has important implications with regard to the present methods that are used in the clinic to assess urethral obstruction or constriction. The resistance as calculated by this model, may be a useful indicator of urethral constriction and obstruction, since it is especially independent of the bladder function. Changes in the urethral elasticity during voiding which are estimated by the model add a new diagnostic parameter to pressure-flow studies.

To investigate the effect of urethral obstruction during late fetal life on renal development and function, we developed a rabbit fetal model of obstructive nephropathy to examine the pathological and biochemical consequences of urethral obstruction and beneficial effects of early surgical decompression. Animals were divided into four groups, i.e., obstructed, early decompressed, late decompressed, and control. Fetal renal development was evaluated by histological examination and counting the number of glomeruli in the four groups. The number of renal glomeruli correlated with gestational age in the normal fetus (r = 0.90, P < 0.0001). Urethral ligation on gestational day 25 (full-term, 31 days) resulted in thinning of the renal cortex and significantly decreased the number of renal glomeruli. The concentration of urinary microalbumin was higher when urethral obstruction was maintained for 3 days than 1 day after urethral obstruction, although urinary beta2- microglobulin, Na, Cl, and osmotic pressure did not change during this period. Decompression of urethral obstruction 1 day after induction of urethral obstruction resulted in improvement in the severity glomerular hypoplasia compared with late decompression (P < 0.01). Our results suggest that the rabbit fetal model simulates fetal urethral obstruction in humans, and indicates that early surgical decompression may be effective in restoration of normal renal function.

Urodynamics include several investigations of the bladder-sphincter complex. Uroflowmetry is easy to perform but interpretation might be hazardous in very young children: in urethral obstruction, it shows a decrease in the maximal flow rate and an increase in the voiding time: such an investigation has no specific value in case of posterior urethral valves since it can be even normal in case of obstruction. Nevertheless, uroflowmetry is of great interest with respect to postoperative follow-up. Other investigations of the bladder and of the urethra are more aggressive and not so helpful in diagnosing obstruction: they might be helpful in understanding and managing persistent voiding disorders after posterior urethral valves section.

The effects of i.v. administration of different drugs utilized in the therapy of detrusor instability have been studied in conscious catheterized female rats with infravesical outflow obstruction induced by partial urethral ligature, in comparison to normal animals. The effects of oxybutynin (1 mg/kg), terodiline (10 mg/kg), and nifedipine (1 mg/kg), were evaluated with regard to bladder capacity (BVC) and micturition pressure (MP) both in normal and obstructed rats. The effects on micturition and residual volume, as well as on spontaneous contractile activity representative of bladder instability, were also observed in obstructed rats. In normal animals, terodiline and oxybutynin induced a significant decrease in micturition pressure without changes in BVC. In obstructed rats, these drugs administered at the same doses did not induce any significant change in all the observed parameters. Nifedipine that in normal rats also reduced the MP, in obstructed animals induced an inhibition of bladder instability (about 50%) with no effects on the other cystometrographic parameters.