Posterior Urethral Valve Patients Research Articles

Role of Urinary Biomarkers (Transforming Growth Factor β1, Neutrophil Gelatinase-Associated Lipocalin, and Cystatin C) as a Prognostic Factor of Renal Outcome in the Posterior Urethral Valve.

The urinary biomarker response precedes the appearance of any renal structural or functional derangement. Transforming growth factor-β1 (TGF-β1), neutrophil gelatinase associated lipocalin (NGAL), and Cystatin C (CysC) can act as the early prognostic markers in posterior urethral valve (PUV) patients. To compare the urinary levels of TGF-β1, NGAL, and CysC between PUV cases and age matched controls and to correlate these with renal structural and functional parameters. This prospective study included children with PUV diagnosed using the standard investigations and an equal number of age-matched controls with nonurological problems. For the study subjects, the urinary samples were collected at three different time points (pre- and postoperatively at 3 and 6 months), whereas for controls, only single-voided samples were studied. The urinary levels of TGF-β1, NGAL, and CysC were estimated by the standardized techniques using the ELISA kits. Statistical methods were used to drive the comparisons between cases and controls. Fifteen children with a median age of 10 (5-48) months were enrolled in each of the two groups. The mean uTGF-β1 in the case group was significantly higher at all three time points (43.20 ± 6.13 pg/ml, 43.33 ± 11.89 pg/ml and 40.71 ± 9.01 pg/ml) as compared to the control group (29.12 ± 8.31 pg/ml) (P ≤ 0.001). The median uNGAL in the case group was also higher (17.78 ng/ml, 2.35 ng/ml and 2.536 ng/ml) as compared to the control group (1.31 ng/ml). However, the difference was significant only preoperatively (P = 0.02). The median uCysC in case group was similarly higher (0.347 μg/ml, 0.439 μg/ml, and 0.382 μg/ml) than the control group (0.243 μg/ml) (P > 0.05). Serum creatinine in the case group (0.49 mg/dl) showed no significant rise above that of control (0.24 mg/dl). A cutoff value of uTGF-β1 = 36.55 pg/ml (P < 0.001), uNGAL = 0.879 ng/ml (P = 0.02), and uCysC = 0.25 μg/ml (P = 0.22) was found to be associated with renal damage in PUV. A significant correlation was found between uNGAL and S. creatinine at 3 months (r = 0.43, P = 0.017) and 6 months (r = 0.47, P = 0.08). The elevated uTGF-β1, a decline in uNGAL and an increase in uCysC suggests ongoing inflammation, improvement in hydronephrosis and a prolonged proximal tubular dysfunction in PUV patients, respectively.

The impact of posterior urethral valves on pediatric quality of life and family function: Prospective analysis of serial patients managed in a dedicated multidisciplinary clinic

Posterior urethral valves (PUV) is a chronic condition that can adversely impact child and family health related quality of life (HRQOL). Surprisingly, to date, the impact of this condition on the QOL of children with PUV has not been studied. Thus, our aim is to evaluate this important aspect of care using validated questionnaires in our institutional PUV clinic. From December 2022 to January 2024, the PedsQL Inventory and associated family impact module was distributed in our PUV clinic. Higher scores reflect better HRQoL and less impact on family. Children >8 years old completed the tool themselves, otherwise parents completed the tools on behalf of the child. We compared PUV scores against reported psychometric data from healthy children and other chronic illnesses. A total of 112 families completed the questionnaires. The total HRQoL score was 80±13. Overall, we noted that the domains reflecting psychosocial impact were significantly lower than those of physical well-being (76±16 vs. 89±15 for psychosocial and physical impact, respectively; p<0.01). There was a significant difference in the psychosocial emotional impact for children managed with clean intermittent catheterization (CIC) compared to those who were not (69±21 vs. 81±16; p=0.005) (Table 2). In addition, we noted that children with PUV scored similar to healthy controls, but higher than children with other chronic illnesses. With respect to the impact on family, overall, parent, and family impacts were 76±19, 78±21, and 81±21, respectively. Chronic illness has been associated with a negative impact on HRQoL in both adults and children. We noted similar findings the present study, particularly for young children and those who are maintained on CIC. To our knowledge, this is the first study to evaluate the impact of PUV on a child's HRQoL as well as the impact on the family, and to document a negative psychosocial impact of CIC in this population. However, there are some important limitations to be addressed including relying on families to complete questionnaires accurately during busy clinic visits and the lack of controls from the same environment. When compared to healthy controls, PUV patients score similarly in HRQoL assessment. In addition, children <3years of age report a negative impact on physical well being, and CIC negatively impacts the emotional well-being. These data can be used to advocate for better mental health supports and social work for these children.

Kidney disease progression in pediatric and adult posterior urethral valves (PUV) patients.

Posterior urethral valves (PUV) is the most common cause of obstructive uropathy in boys; approximately 15% develop kidney failure by early adulthood. However, rates of kidney function decline are poorly defined in PUV children and adults, as is the impact of potentially modifiable chronic kidney disease (CKD) progression risk factors. We conducted a retrospective review of all PUV patients followed at our institution from 1995 to 2018. Inclusion criteria were estimated glomerular filtration rate (eGFR) > 20ml/min/1.73 m2 after 1year of age, no dialysis or kidney transplant history, and ≥ 2 yearly serum creatinine values after age 1year. eGFRs were calculated using creatinine-based estimating formulas for children (CKID U25) or adults (CKD-EPI). The primary outcome was annualized change in eGFR, assessed with linear mixed effects models. We also examined the association of acute kidney injury (AKI), proteinuria, hypertension (HTN), and recurrent febrile urinary tract infections (UTIs) with eGFR decline. Fifty-two PUV patients met the inclusion criteria. Median (interquartile range) eGFR decline was 2.6 (2.1, 3.1) ml/min/1.73 m2/year. Children (n = 35) and adults (n = 17) demonstrated progressive decline. Proteinuria and recurrent UTIs were significantly associated with faster progression; AKI and HTN were also associated but did not reach significance. PUV patients show progressive loss of kidney function well into adulthood. Proteinuria and recurrent UTIs are associated with faster progression, suggesting potential modifiable risk factors. This is the first study to report annualized eGFR decline rates in PUV patients, which could help inform the design of clinical trials of CKD therapies.

Assessing the Utility of Tamsulosin in Delaying Progression to Clean Intermittent Catheterization and End-stage Renal Disease in Patients With Posterior Urethral Valves: Are We Postponing the Inevitable?

To assess whether tamsulosin may aid emptying of the lower urinary tract in posterior urethral valves patients, mitigating the likelihood of progressing to clean intermittent catheterization (CIC) or need for renal replacement therapy. We reviewed a prospective institutional database containing posterior urethral valves patients treated between January 2000 and January 2022. After assessing baseline characteristics, Kaplan-Meier survival curves and log-rank tests were generated to assess differences in clinically significant outcomes (progression to CIC, dialysis, or kidney transplantation) between those prescribed tamsulosin and those who were not. A total of 179 patients were included. Fifty-nine patients received tamsulosin prior to initiation of CIC (group 1), and 120 did not (group 2). The baseline characteristics were similar between the two groups, except for anticholinergic use (tamsulosin group - 35/59 vs no tamsulosin - 32/120, P<.001). The median age at tamsulosin initiation was 26.0 months (IQR 15.5-48.6) and the median time from initiation of tamsulosin to progression to CIC was 52.6 months (IQR 10.1-69.3). Kaplan-Meier survival curves showed that patients on tamsulosin were less likely to progress to CIC (P=.021), however, there was no difference in progression to dialysis or kidney transplantation. A Cox-regression analysis controlling for baseline characteristics, including age, anticholinergic use, vesicoureteral reflux severity, and CKD stage at 1-year of life, showed a consistent effect of tamsulosin in delaying progression to CIC (HR 0.444 95%CI 0.218-0.902, P=.025). While tamsulosin may delay CIC, it does not appear to delay progression to end-stage renal disease. Additional studies exploring specific patient factors are required to determine the timing and subset who may benefit the most from tamsulosin.

Posterior urethral valves in patients with trisomy 21: Similar renal outcomes and rates of volitional voiding

Posterior urethral valves (PUV) occur in patients with Down Syndrome (DS) at a rate of 3-4%; far higher than the general population. Our understanding of the relationship between PUVs and DS is in its infancy, with the majority of the literature consisting of case reports. In this study, we present the largest known series of DS patients with PUVs. We hypothesized that patients with DS and PUVs would have worse functional bladder outcomes and renal outcomes when compared to PUV patients without DS. We queried our prospectively managed multi-institutional database of PUV patients from 1990 to 2021. We identified patients with a concomitant diagnosis of DS and PUV. In addition, we performed a systematic review of the literature describing the presentation of children with PUV and DS. Patient demographics, renal outcomes, voiding habits, surgical interventions, and radiologic images were aggregated and analyzed. Out of the 537 patients in our PUV database, we identified 18 patients with a concomitant diagnosis of PUV and DS, as well as 14 patients with a concomitant diagnosis of PUV and DS from the literature. DS and non-DS patients had a similar age at presentation, 31.5 days (2-731) and 17 (4-846), and length of follow up 6.32 years (2-11.2) and 6.98 (1-13). Both groups had similar nadir creatinines DS 0.43 (0.4-0.8), non-DS 0.31 (0.2-0.5) and similar rates of renal failure (DS 11.1% and non-DS 14.5%). With respect to bladder outcomes, a similar percentage of patients were volitionally voiding at last follow up (DS 72.2% and non-DS 72.3%). Our literature review corroborated these findings. Patients with DS and PUV have similar renal outcomes to other PUV patients in terms of renal function, progression to renal failure, and probability of volitional voiding with continence. Given the increased rate of PUVs in the DS population, physicians should have a high index of suspicion for PUV when patients with DS present with voiding dysfunction.

Surrogate imaging markers of Urodynamic proven bladder dysfunction in posterior urethral valves: A comprehensive evaluation

Although urodynamic evaluation forms the cornerstone of diagnosis and management of bladder dysfunction in posterior urethral valves (PUV), yet it could be helpful to learn if there are any non-invasive surrogate imaging markers for the same. To study the diagnostic accuracy of various imaging surrogate markers of urodynamic proven bladder dysfunction in PUV. This cross-sectional study over two years included 38 children of endoscopically proven PUV. Based on bladder function on Urodynamics the patients were divided into 2 groups: Group 1: PUV with normal bladder function (n: 17, 44.7%); Group 2: PUV with impaired bladder function (n: 21, 55.3%). Voiding dysfunction, incidence of recurrent urinary tract infection (UTI), polyuria, grade of hydronephrosis, retrovesical ureteric diameter (mm) and detrusor wall thickness (DWT mm) was compared in the two groups. MCU at initial presentation and post definitive treatment was studied and a bladder hostility score (BHS) was assigned to each patient and compared in the two groups. Correlation between impaired bladder function and clinical and radiological variables was performed by using Spearman Rank correlation and data receiver operating curves (ROC) were plotted to identify the critical values predicting the probability of bladder dysfunction in PUV. Mean age at evaluation was 6.1±4.2 years with a mean follow-up of 5±3.9 years (median: 3.5 years). Voiding dysfunction, persistent or worsening grade III and IV hydroureteronephrosis, retrovesical ureter diameter ≥13.1mm (diagnostic accuracy: 68.4%, AUC: 0.738), DWT on full bladder ≥1.85mm (diagnostic accuracy: 81.6%, AUC: 0.846) and pretreatment BHS ≥5.5 (diagnostic accuracy: 71.4%, AUC: 0.763) were the clinical and imaging predictors of impaired bladder function. Comparative analysis of the two groups is as shown in table. Clinical and imaging parameters are unable to convincingly identify the type of bladder dysfunction which is often required to manage PUV patients appropriately. Increased detrusor wall thickness suggests underlying bladder dysfunction and while those with small capacity hypertonic bladders have higher mean detrusor wall thickness than those with myogenic failure, the difference was not statistically significant (p: 0.41). Attempts to predict underlying bladder dysfunction by MCU imaging may be erroneous in nearly one-third of the patients. Thus, these imaging parameters are complementary and sequential to urodynamic, which certainly continues to be the gold standard investigation to assess bladder dysfunction in PUV.

MP53-14 RENAL FUNCTION BY EGFR CALCULATORS IN PRUNE BELLY SYNDROME AND POSTERIOR URETHRAL VALVES

You have accessJournal of UrologyCME1 Apr 2023MP53-14 RENAL FUNCTION BY EGFR CALCULATORS IN PRUNE BELLY SYNDROME AND POSTERIOR URETHRAL VALVES Alexandra Carolan, Shane Batie, Samuel Gold, Shaheer Ali, Daniel Wong, Nida Karra, Nathalia Amado, Jyothsna Gattineni, Bruce Schlomer, Yvonne Chan, and Linda Baker Alexandra CarolanAlexandra Carolan More articles by this author , Shane BatieShane Batie More articles by this author , Samuel GoldSamuel Gold More articles by this author , Shaheer AliShaheer Ali More articles by this author , Daniel WongDaniel Wong More articles by this author , Nida KarraNida Karra More articles by this author , Nathalia AmadoNathalia Amado More articles by this author , Jyothsna GattineniJyothsna Gattineni More articles by this author , Bruce SchlomerBruce Schlomer More articles by this author , Yvonne ChanYvonne Chan More articles by this author , and Linda BakerLinda Baker More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003301.14AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: In prune belly syndrome (PBS), prior comparison of estimated glomerular filtration rate (eGFR) with calculators using creatinine (Cr) and/or Cystatin C (Cys) showed lower mean eGFR with Cys-based calculators than with the “Bedside Schwartz” Cr-based calculator (eGFRcr) in Chronic Kidney Disease (CKD) 1 and 2. As abdominal skeletal muscle paucity in PBS could reduce serum Cr, we hypothesized the differences in mean eGFRcr and eGFR by Cys-based calculators (denoted as Δ) will be greater in PBS compared to posterior urethral valves (PUV), with intact musculature. METHODS: A 2014-2021 retrospective ICD-10 search identified PBS and PUV patients with labs and height without neuromuscular disorders or renal replacement. eGFRcr, eGFRcys and creatinine-cystatin C-based GFR (eGFR-CKiD) were calculated. CKD stages were assigned by eGFRcr. Δ eGFRcr, eGFRcys, and eGFR-CKiD between PBS and PUV were compared with t-test. Those with normal Cr and/or Cys but who had CKD by eGFR calculators were identified. The proportion of changes in CKD staging by each calculator was compared with chi-square or Fishers exact test. RESULTS: 95 PUV and 26 PBS patients were analyzed (Figure 1). Δ eGFRCr and eGFR with Cys-based calculators by CKD stage or by all CKD stages combined were not different between PBS and PUV. By all CKD stages combined, Δ eGFRcr and eGFRcys was 18 and 13 mL/min/1.73 m2 in PBS and PUV, respectively (p=0.22) and Δ eGFRcr and eGFR-CKiD was 8 and 5 ml/min/1.73 m2 in PBS and PUV, respectively (p=0.71). Among patients with normal Cr and/or Cys, at least 25% had CKD2-3 by eGFR calculation. Changes in CKD stage by Cys-based calculators compared to eGFRcr were not significantly different between PBS and PUV (p>0.3). Upstaging was most frequent in PBS and PUV CKD1 and 2. CONCLUSIONS: Differences between eGFRcr and eGFR by Cys-based calculators in PBS and PUV patients were not significant, suggesting paucity of abdominal musculature in PBS may not account for the lower eGFRs observed using Cys-based calculators. In 25% of patients, normal Cr and/or Cys actually had CKD2-3, highlighting importance of eGFR calculation. Cys-based calculators upstaged, especially in CKD1 and 2. Cys-based eGFRs calculators should be considered for early identification of CKD in patients with congenital urologic abnormalities prone to renal dysfunction. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e717 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alexandra Carolan More articles by this author Shane Batie More articles by this author Samuel Gold More articles by this author Shaheer Ali More articles by this author Daniel Wong More articles by this author Nida Karra More articles by this author Nathalia Amado More articles by this author Jyothsna Gattineni More articles by this author Bruce Schlomer More articles by this author Yvonne Chan More articles by this author Linda Baker More articles by this author Expand All Advertisement PDF downloadLoading ...

MP53-13 DOES THE PRESENCE OF PRESSURE "POP-OFFS" IMPACT VOIDING EFFICIENCY AND BLADDER OUTCOMES IN POSTERIOR URETHRAL VALVES?

You have accessJournal of UrologyCME1 Apr 2023MP53-13 DOES THE PRESENCE OF PRESSURE "POP-OFFS" IMPACT VOIDING EFFICIENCY AND BLADDER OUTCOMES IN POSTERIOR URETHRAL VALVES? Adree Khondker, Priyank Yadav, Jin Kyu Kim, Michael Chua, Natasha Brownrigg, Juliane Richter, Joana Dos Santos, Armando Lorenzo, and Mandy Rickard Adree KhondkerAdree Khondker More articles by this author , Priyank YadavPriyank Yadav More articles by this author , Jin Kyu KimJin Kyu Kim More articles by this author , Michael ChuaMichael Chua More articles by this author , Natasha BrownriggNatasha Brownrigg More articles by this author , Juliane RichterJuliane Richter More articles by this author , Joana Dos SantosJoana Dos Santos More articles by this author , Armando LorenzoArmando Lorenzo More articles by this author , and Mandy RickardMandy Rickard More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003301.13AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The protective role of pressure pop-offs, consisting of vesicoureteral reflux (VUR) and ipsilateral kidney dysplasia, in posterior urethral valve (PUV) is controversial. While there has been significant emphasis on exploring the non-significant association between “pop-offs” and kidney function, there is paucity of data on the impact of this mechanism on bladder function. Here, we analyzed this association by examining the role of pressure pop-offs on long-term bladder outcomes in PUV patients. METHODS: A retrospective chart review was conducted for toilet-trained children with PUV managed at our institution between 2000 and 2022, only excluding cases without recorded uroflowmetry studies. Patients were stratified by the presence of pressure pop-offs (high-grade VUR+ipsilateral kidney dysplasia). Outcomes included uroflowmetry parameters and initiation of clean-intermittent catheterization (CIC). Survival analysis was conducted to calculate hazard ratios (HR). RESULTS: We identified a total of 101 patients who met study inclusion criteria, with a median follow-up of 114 months (IQR 67, 169). The median age of first and last uroflowmetry was 57 months (IQR 48, 82) and 120 months (IQR 89, 160), respectively. Patients with pressure pop-offs had similar flow velocity, post-void residuals, and bladder voiding efficiency to other PUV patients at last follow-up uroflowmetry. On survival analysis, patients with pressure pop-offs had no significant difference in risk of requiring CIC compared to patients without pop-offs (HR 1.92, p=0.06). Kidney dysplasia was independently associated with increased risk of CIC (HR 3.16, p=0.02) while VUR was not (HR 1.85, p=0.07). CONCLUSIONS: We show that boys with pressure pop-offs are not at higher risk of poorer voiding and intermittent catheterization than others with PUV. By extension, VURD syndrome does not confer protection against poorer bladder function. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e717 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Adree Khondker More articles by this author Priyank Yadav More articles by this author Jin Kyu Kim More articles by this author Michael Chua More articles by this author Natasha Brownrigg More articles by this author Juliane Richter More articles by this author Joana Dos Santos More articles by this author Armando Lorenzo More articles by this author Mandy Rickard More articles by this author Expand All Advertisement PDF downloadLoading ...

Posterior Urethral Valve: Factors Affecting the Renal Outcome

Background: Posterior urethral valve (PUV) is the most common cause of lower urinary tract obstruction in male children with associated sequlae. Different factors, such as age at presentation, initial and nadir serum creatinine, renal parenchymal echogenicity on initial USG, vesicoureteric reflux (VUR) , recurrent UTI, bladder dysfunction and the presence or absence of pop-off mechanism like VURD have significant impact on ultimate renal outcome. The main aim of the study was to observe the effects of different prognostic factors like age of presentation and preoperative VUR of the PUV respondents on postoperative long term renal outcome as well as changes of renal function status on the basis of initial and postoperative serum creatinine level in our settings. Material Methods: This was a quasi-experimental study and conducted in the Department of Pediatric urology of Bangladesh Shishu Hospital and Institute, Dhaka. We enrolled 58 male children of different ages having posterior urethral valve, who were admitted in the pediatric urology department from July,2018 to Dec,2021. Results: Total 58 patients included in our study. Among all patients 53.4% were aged between 1 month to 1 year, 39.7% of them were more than 1 year old and 6.9% of them were neonates. Among 31 respondents, 32.3 % had poor renal function 35.5 % of them also had moderately impaired renal function. Again, out of 23 respondents, 30.4% had poor renal function 6% had moderately impaired renal function. The relation between age category and postoperative renal function status (On the basis of postoperative eGFR) of the posterior urethral valve respondents were statistically not significant. Patients who had no VUR, 66.7% of them had normal renal function, 25% had moderately impaired renal function and 8.3% had poor renal function. Respondents who had bilateral VUR, 55% of them had poor renal function and 35% had moderately impaired renal function. Among respondents who had unilateral VUR, 28.6% of them had poor renal function and 28.6% had moderately impaired renal function but 42.9% had normal renal function. The relation between preoperative VCUG findings and postoperative long term renal function status of the PUV patients were statistically significant. 7 (100%) respondents who had preoperative abnormal renal function, more than 71.4% of them had returned to normal renal function after operative procedure. But abnormal renal function was present in 2 (28.6%) patients during follow up. In our study we found 29.3% of our patients had poor renal outcome and 29.3% patients had moderately impaired renal function within the mean follow up period of 19.33±12.38 months (ranges from 9months to 4 years). Conclusion: Our research highlights the significance of age at presentation, despite its statistically negligible effect on long-term renal outcomes. However, among the children with PUV following valve ablation and with a long-term follow-up, beginning serum creatinine and the presence of various types of VUR on initial VCUG had a significant effect (p.05) on postoperative renal function on the basis of serum creatinine.

MP53-19 URINARY MICRORNAS ARE POTENTIAL BIOMARKERS OF SEVERITY OF URINARY TRACT DYSFUNCTION IN PATIENTS WITH POSTERIOR URETHRAL VALVES

You have accessJournal of UrologyCME1 Apr 2023MP53-19 URINARY MICRORNAS ARE POTENTIAL BIOMARKERS OF SEVERITY OF URINARY TRACT DYSFUNCTION IN PATIENTS WITH POSTERIOR URETHRAL VALVES Elizabeth Mann, Melissa Mogle, Aditi Paranjpe, Marion Schulte, and Pramod Reddy Elizabeth MannElizabeth Mann More articles by this author , Melissa MogleMelissa Mogle More articles by this author , Aditi ParanjpeAditi Paranjpe More articles by this author , Marion SchulteMarion Schulte More articles by this author , and Pramod ReddyPramod Reddy More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003301.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Current management strategy for patients presenting with posterior urethral valves (PUV) includes monitoring of renal function to determine when urinary tract (UT) intervention such as intermittent catheterization or urinary diversion is indicated. The challenge with this approach is that ongoing renal injury may no longer be reversible and exposes the child to progression of chronic kidney disease (CKD). We hypothesize that microRNAs (miRNA) derived from urinary small extracellular vesicles (sEV) reflect the physiological status of the UT and may serve as real-time indicators of lower urinary tract injury. These biomarkers could permit the development of a proactive strategy of serial monitoring of the lower UT in patients with PUV and permit timely intervention prior to the progression of renal injury. METHODS: We have undertaken an IRB approved prospective study. Informed consent was obtained at time of enrollment. Urine samples are collected for each patient at least once a year and urinalysis performed. We excluded samples with active infections. Patients (1-18 yrs) with PUV were stratified into clinical categories based on the severity of the involvement of their UT. Patients with isolated genital pathology and a normal UT served as negative controls. sEVs were isolated from the urine by ultracentrifugation and total RNA extracted. Next-generation small RNA sequencing and differential expression analysis was performed. RT-qPCR was used to verify the expression of candidate miRNAs. RESULTS: A total of 76 PUV Patients and 35 controls have been enrolled in the study, with 244 urine samples collected. Principle component analysis of the most variable miRNAs demonstrated a clear clustering of the patients in the moderate/severe category compared to the patients with mild disease and non-PUV controls. We have identified 61 miRNAs that were upregulated and 45 miRNAs that were downregulated in the moderate/severe patients (≥1.5-fold, p≤0.05). We selected 4 miRNAs to analyze further by RT-qPCR and confirmed the decreased expression of miRNA-30a-5p in moderate/severe cases (>5-fold, p≤0.01). CONCLUSIONS: This study demonstrates that urinary miRNAs can serve as biomarkers of the severity of UT dysfunction in patients with PUV. Ongoing studies seek to further validate these findings. The development of a noninvasive urinary assay for a set of predictive miRNA biomarkers will enhance our ability to care for patients with PUV and enable real-time assessment of the health of their lower urinary tract. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e719 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Elizabeth Mann More articles by this author Melissa Mogle More articles by this author Aditi Paranjpe More articles by this author Marion Schulte More articles by this author Pramod Reddy More articles by this author Expand All Advertisement PDF downloadLoading ...

Does VURD syndrome impact voiding efficiency in posterior urethral valves?

There is debate regarding the effect of VURD syndrome, consisting of vesicoureteral reflux (VUR) and ipsilateral kidney dysplasia, on long-term outcomes in boys with posterior urethral valve (PUV). Here, we assessed whether VURD syndrome played a "protective" role on long-term bladder outcomes and voiding efficiency in boys with PUV. A retrospective chart review was conducted for toilet-trained children with PUV managed at our institution between 2000 and 2022, only excluding cases without recorded uroflowmetry studies. Patients were stratified by VUR status and by the presence of VURD syndrome (high-grade VUR+ipsilateral kidney dysplasia). Outcomes included initial and final uroflowmetry parameters, and initiation of clean-intermittent catheterization (CIC). We identified a total of 101 patients who met study inclusion criteria, with an overall median follow-up of 114 months (IQR 67, 169). The median age of first and last uroflowmetry was 57 months (IQR 48, 82) and 120 months (IQR 89, 160), respectively. Patients with VURD syndrome had similar flow velocity, post-void residuals, and bladder voiding efficiency to other PUV patients at last follow-up uroflowmetry. On survival analysis, patients with VURD syndrome had no significant difference in risk of requiring CIC compared to patients without pop-offs (p=0.06). Like more contemporary studies on pressure pop-offs, we show that this population is not at higher risk of poorer voiding and intermittent catheterization than others. VURD syndrome does not confer protection against poorer bladder function. Instead, our study suggests an independent association between kidney dysplasia and bladder outcomes which requires further attention. Among boys with PUV, VURD syndrome was not associated with significantly different uroflowmetry findings or rates of CIC by last follow-up.

The Outcome of Posterior Urethral Valves among Children in Tertiary Care Hospital–A Prospective Study

Introduction: Posterior Urethral Valve (PUV) is the most common cause of lower urinary tract obstruction in male children. This obstruction in posterior urethra could lead to severe dilatation of upper urinary tract and functional impairment of one or both kidney. The presentations are not always same for all patients. Early diagnosis and appropriate treatment may reduce the progressive damage and helps in recovery. Aim of the Study: The aim of this study was to find out the presentation and to assess the short term functional outcome after fulgaration of the patients with PUV. Methods: This prospective study was conducted at Pediatric urology department, Bangladesh Shishu Hospital and Institute, Dhaka. We included fifty patients with Posterior urethral valve, who were treated at the pediatric urology department from Jan, 2019 to Nov, 2021. Result: Total 50 patients enrolled in the study. In our study we found 50% of our patients were aged between 1 month to 1 year, followed by 36% were more than 1 years old and 14% were less than 1 month old. 76% patients were presented with dribbling of urine. 40%,26%,10% and 6% patients had UTI, poor stream,, retention of urine and palpable bladder respectively. 45 patients had bilateral hydronephrosis ( HDN) at presentation and only 5 had unilateral hydronephrosis in USG. At follow up MCU, 14% patients had unilateral VUR and 10% patients had bilateral VUR. Mean postoperative serum creatinine was 0.585 mg/dl. We found residual Valve in 11(22%) patients during follow up who required repeat Valve ablation. Conclusion: In our study, we found that Cystoscopic valve ablation and follow up is the treatment of choice for PUV patients which may arrest the progressive damage of renal function and facilitate the improvement. Further multicenter study and long term follow up is necessary for understanding the ultimate outcome.

Frequency of posterior urethral valves in newborns with hydronephrosis in nicu and early outcomes: A tertiary center experience

Aim: To assess the frequency of posterior urethral valves (PUV) in male infants diagnosed with hydronephrosis in the neonatal intensive care unit (NICU) and the early outcomes. Materials and Methods: The study included male patients who had been diagnosed with hydronephrosis in the antenatal or postnatal period in our NICU between 2017 and 2020. We investigated antenatal hydronephrosis detection statuses, birth histories, ultrasonographic findings, and the lowest creatinine values detected during the NICU treatment of PUV-diagnosed patients. Results: A total of 73 infants had hydronephrosis and 20.5% of the patients (n=15) had PUV, and 26.6% (n=4) of the PUV patients had below 5 mm renal pelvic diameters. These patients were diagnosed with clinical suspicion (interrupted urination, decreased diuresis, or globe vesicle). In PUV-diagnosed patients, dysplastic kidneys and increased renal echogenicity are associated with poor outcomes (death or dialysis need). Conclusion: Hydronephrosis finding in ultrasonography may not be sufficient, so complete clinical evaluation is needed in newborns not to miss PUV cases.

Relation between blood levels of heavy metals and some markers of oxidative stress among boys with neuropathic bladder and posterior urethral valve

BackgroundThe status of heavy metals in children with lower urinary tract pathology that may harm the upper tract, e.g., neuropathic bladder and posterior urethral valve and its relationship with oxidative stress has not been adequately investigated. Therefore, the object of the current work was to evaluate the concentrations of copper, zinc, cadmium and lead and their relations with levels of catalase (CAT), malondialdehyde (MDA) and glutathione (GSH) in boys with neuropathic bladder and posterior urethral valve. MethodsThirty-six children with neuropathic bladder, 35 children with posterior urethral valve and 33 health controls were included in the study. In addition to routine laboratory tests, blood samples were collected from patients and controls to assess levels of Cu, Zn, Cd and Pb in addition to plasma concentrations of CAT, MDA and GSH. ResultsSignificantly elevated levels of Cu, Pb, CAT, MDA and GSH and significantly lower concentration of blood Zn were found in the studied groups compared to the controls. In the posterior urethral valve group, blood level of Cu was positively correlated with GSH while a significantly negative relation was observed between blood Zn and CAT activity among the neuropathic bladder patients. ConclusionNeuropathic bladder and posterior urethral valve may lead to abnormalities in the blood levels of heavy metals (i.e. Cu, Pb and Zn) and markers of oxidative stress (CAT, MDA and GSH). Therefore, the levels of theses metal ions should be monitored during the treatment course of neuropathic bladder and posterior urethral valve patients to prevent or minimize long-term oxidative injury.

Long-term Follow Up of Posterior Urethral Valve Patients and Predictors of Outcome, Cairo University Specialized Pediatric Hospital

Long-term Follow Up of Posterior Urethral Valve Patients and Predictors of Outcome, Cairo University Specialized Pediatric Hospital

Chronic Kidney Disease in Boys with Posterior Urethral Valves-Pathogenesis, Prognosis and Management.

Posterior urethral valves (PUV) are the most common form of lower urinary tract obstructions (LUTO). The valves can be surgically corrected postnatally; however, the impairment of kidney and bladder development is irreversible and has lifelong implications. Chronic kidney disease (CKD) and bladder dysfunction are frequent problems. Approximately 20% of PUV patients will reach end-stage kidney disease (ESKD). The subvesical obstruction in PUV leads to muscular hypertrophy and fibrotic remodelling in the bladder, which both impair its function. Kidney development is disturbed and results in dysplasia, hypoplasia, inflammation and renal fibrosis, which are hallmarks of CKD. The prognoses of PUV patients are based on prenatal and postnatal parameters. Prenatal parameters include signs of renal hypodysplasia in the analysis of fetal urine. Postnatally, the most robust predictor of PUV is the nadir serum creatinine after valve ablation. A value that is below 0.4 mg/dl implies a very low risk for ESKD, whereas a value above 0.85 mg/dl indicates beneficial kidney outcome. Experimental urinary markers such as MCP-1 and TGF-β, as well as microalbuminuria, indicate progression to CKD. Until now, prenatal intervention may improve survival but yields no renal benefit. The management of PUV patients includes control of bladder dysfunction and CKD treatment to slow down progression by controlling hypertension, proteinuria and infections. In kidney transplantation, aggressive bladder management is essential to ensure optimal graft survival.

Posterior urethral morphology on initial voiding cystourethrogram correlates to early renal outcomes in infants with posterior urethral valves

Posterior urethral valves (PUV) is a leading cause of chronic renal failure in childhood. Bladder and posterior urethral deformity in infants with PUV are highly variable on initial voiding cystourethrogram (VCUG). Some types of deformity may be more important than others in determining the severity of the condition. Identification of specific VCUG features may allow for a simple, early screening assessment for patients. Determine whether morphologic features on the initial VCUG correlate to renal outcomes as measured by the creatinine nadir in the first year after ablation. Children with PUV treated by primary valve ablation before 12 months old and followed >1 year were identified. Initial diagnostic VCUG was evaluated for the bladder height to width ratio (HW-B), posterior urethral height to width ratio (HW-PU), and posterior-anterior urethral ratio (PA-UR). A trabeculation grade was assigned by three pediatric urologists, and reflux was noted. Univariable analyses with chi-square and t-test were used to compare bladder and posterior urethral morphology factors among those who obtained a creatinine nadir <0.8 or ≥0.8mg/dL in the first year after ablation. Linear regression was performed to correlate morphology values with true creatinine nadir. A total of 120 boys were ablated at mean age of 40.5 days (range 0-342) and followed for 5.9 years (± 3.85). Among these, 21 (17.5%) had a creatinine nadir ≥0.8mg/dL. Mean overall HW-B and mean PA-UR were not significantly different between those with creatinine nadir <0.8 versus ≥0.8mg/dL. Bladder trabeculation grade was not associated with creatinine nadir. For the entire cohort, only the difference in HW-PU was statistically significant between creatinine nadir groups with a much higher ratio among those with a nadir ≥0.8 (p<0.001). Linear regression demonstrated a significant positive correlation between the HW-PU and creatinine nadir (R 2=0.097, p=0.002). The presence of bilateral reflux is significantly associated with creatinine nadir ≥0.8mg/dL (p=0.001). We investigate for the first time the association of morphology features on the initial VCUG with renal outcome in PUV patients. Posterior urethral deformity as quantified by a higher HW-PU ratio is significantly correlated with a higher creatinine nadir, whereas measured bladder morphology metrics are not. HW-PU may be an indirect measure of the severity of obstruction in posterior urethral valves. The HW-PU appears to be a meaningful early morphologic metric for renal outcome.

Outcome of boys with posterior urethral valves from a single tertiary hospital in Singapore.

Posterior urethral valve (PUV) is the most common congenital cause of bladder outflow obstruction in male infants. Despite timely treatment, renal damage can still occur in the long-term leading to chronic kidney disease (CKD). A retrospective review of all PUV patients in a single tertiary institution between April 1998 and July 2019 was conducted to analyze their presentations, management and outcomes. Long-term renal function, radiologic scans and somatic growth were evaluated. A total of 16 patients were included in this study. Two patients who defaulted all follow-ups were excluded. Seven patients (43.7%) presented in the antenatal period; four patients (25%) presented in the neonatal period and five patients (31.3%) presented in the post-neonatal period. Primary transurethral fulguration of valves was done in 13 patients, while three had vesicostomies as the primary procedure. Three patients had associated anterior urethral valves (AUV), which were treated endoscopically. Nine boys had additional procedures for diversion and undiversion, VUR, non-functioning kidney and clean intermittent catheterization. Ten patients had urodynamic studies performed, of which eight patients received anticholinergic therapy. Eleven patients had DMSA scans, of which three patients had a normal study and eight patients showed unilateral reduced function. Four patients were diagnosed with CKD on long-term follow-up duration over 5 years. All patients were shown to have good somatic growth. Patients with PUV can suffer from complications despite primary treatment. In our small cohort, a quarter of our patients developed CKD on follow-up. Thus, patients need long-term follow-up to optimize bladder and renal function.

Correlation of Urethral Ratio and Bladder Wall Thickness with Cystoscopic Findings in Posterior Urethral Valve Patients to Assess Residual Valves.

Introduction:Posterior urethral valve (PUV) is life threatening congenital anomaly of urinary tract. Aim of the study was to correlate urethral ratio (UR) and bladder wall thickness (BWT) with cystoscopic findings in PUV patients to assess residual valves and to validate UR as a diagnostic tool for residual valves. It also aimed to assess the utility of bladder wall thickness in diagnosis of residual valves.Materials and Methods:A total of 31 patients were included in the prospective study done from 2017 to 2019. Calculation of UR was done in oblique VCUG films by dividing maximum posterior and anterior urethral diameter without the catheter insitu. Measurement of BWT was done at dome and bladder neck at full distension with feeding tube insitu and was done at same volume in follow up. The procedure was repeated at 3 months follow up. The findings were compared with cystoscopic findings for the status of residual valves as gold standard. Each patient served as control for self in the study.Results:Median age of presentation was 1 years with range of 1day to 10 years. The most common complains at the time of presentation in our study was straining (35.48%) followed by antenatally diagnosed patients (25.81%) and recurrent UTI (19.36%). Pre fulguration median UR was 2.45. Post Fulguration median UR was 1.20. It showed a statistically significant reduction (p < 0.001) after fulguration. Pre fulguration median BWT was 4 mm. Post fulguration median BWT was 2.5 mm. BWT showed a statistically significant reduction (p < 0.001) after fulguration as well. ROC curve was plotted for UR and BWT. BWT more than 1.95 mm (sensitivity-80%) and UR more than 1.2 (sensitivity-70%) indicates residual valves.Conclusion:A step ladder approach including BWT, UR and check cystoscopy can serve as a new diagnostic algorithm for the assessment of residual valves thereby avoiding extra radiation and general anesthesia exposure.

Serum and urine periostin and cytokeratin-18 in children with congenital obstructive nephropathy.

Congenital obstructive nephropathy (CON) is one of the most common causes of chronic kidney disease in children. The aim of the study was to investigate serum and urine periostin and cytokeratin-18 (CK-18) in children with CON in relation to CON etiology, treatment, and kidney injury. We evaluated 81 children with CON secondary to ureteropelvic junction obstruction (UPJO), ureterovesical junction obstruction (UVJO), posterior urethral valves (PUV) and 60 controls. Neither biomarker demonstrated any relation to CON etiology. However, all patients showed significantly higher urine periostin (uPeriostin) and uPeriostin/Cr levels than the controls. Also, UVJO patients showed higher sCK-18 and uCK-18/Cr levels, and PUV patients showed higher uCK-18/Cr levels than the controls. Neither biomarker was found to have any relation to CON treatment. However, conservatively treated children and those before and after surgery showed significantly higher uPeriostin and uPeriostin/Cr levels than the controls. uPeriostin strongly correlated with differential renal function (DRF) < 40%. The ROC analysis demonstrated the best area under the curve (AUC) for uPeriostin (0.831) and uPeriostin/Cr (0.768), and low for sPeriostin (0.656) and uCK-18 (0.615) for detecting renal injury. In conclusion, although serum and urine periostin and CK-18 did not display any relation to etiology or the type of CON treatment, uPeriostin seems to be a useful tool for detecting renal injury in children with CON, especially due to its strong negative correlation with DRF < 40%.