Predictive factors for survival in patients with oligohydramnios secondary to antenatal kidney disease.

BACKGROUND: Renal oligohydramnios (ROH) is caused by bilateral congenital abnormalities, either of renal parenchymal or obstructive origin. ROH is a poor prognostic factor of neonatal survival; lung hypoplasia is reported to be the main cause of mortality. We aimed to describe the fetal morbidity and pre- and postnatal mortality in case of ROH due to renal congenital pathologies and to find predictive risk factors for morbidity and mortality. METHODS: All data were collected in Trousseau Hospital in the obstetric, neonatology, and pediatric nephrology units, from 2008 to 2020. RESULTS: We included 66 fetuses with renal parenchymal pathologies posterior urethral valves (PUV) (N = 25), bilateral kidney agenesis (N = 10), hypodysplasia (N = 16), and polycystic kidney disease (N = 10) causing oligohydramnios identified on antenatal ultrasound. Total pre- and postnatal mortality was 76% (50/66). Mortality, excepting termination of pregnancy (TOP), was 65%. The presence of pneumomediastinum and pneumothorax was not different in survivors and non-survivors. Fetuses with kidneys having features of hypodysplasia on ultrasound at T2 and those with oligohydramnios before 32 weeks GA had a higher risk of death. There was a significant difference in plasma creatinine of the surviving patients compared to the deceased patients, from day 3 onwards (183 µmol/L [88; 255] vs. 295 µmol/L [247; 326]; p = 0.038). CONCLUSIONS: The main differences between survivors and non-survivors among patients with "renal oligohydramnios" were oligohydramnios detection before 32 weeks GA, dysplasia detection on the second trimester ultrasound, and increase of serum creatinine from day 3 onwards. A higher resolution version of the Graphical abstract is available as Supplementary information.

Deep learning imaging features derived from kidney ultrasounds predict chronic kidney disease progression in children with posterior urethral valves.

BACKGROUND: We sought to use deep learning to extract anatomic features from postnatal kidney ultrasounds and evaluate their performance in predicting the risk and timing of chronic kidney disease (CKD) progression for boys with posterior urethral valves (PUV). We hypothesized that these features would predict CKD progression better than clinical characteristics such as nadir creatinine alone. METHODS: We performed a retrospective cohort study of boys with PUV treated at two pediatric health systems from 1990 to 2021. Features of kidneys were extracted from initial postnatal kidney ultrasound images using a deep learning model. Three time-to-event prediction models were built using random survival forests. The Imaging Model included deep learning imaging features, the Clinical Model included clinical data, and the Ensemble Model combined imaging features and clinical data. Separate models were built to include time-dependent clinical data that were available at 6 months, 1 year, 3 years, and 5 years. RESULTS: Two-hundred and twenty-five patients were included in the analysis. All models performed well with C-indices of 0.7 or greater. The Clinical Model outperformed the Imaging Model at all time points with nadir creatinine driving the performance of the Clinical Model. Combining the 6-month Imaging Model (C-index 0.7; 95% confidence interval [CI] 0.6, 0.79) with the 6-month Clinical Model (C-index 0.79; 95% CI 0.71, 0.86) resulted in a 6-month Ensemble Model that performed better (C-index 0.82; 95% CI 0.77, 0.88) than either model alone. CONCLUSIONS: Deep learning imaging features extracted from initial postnatal kidney ultrasounds may improve early prediction of CKD progression among children with PUV. A higher resolution version of the Graphical abstract is available as Supplementary information.

Implementation of a standardized clinical pathway in a dedicated posterior urethral valves clinic: short-term outcomes.

BACKGROUND: To determine if the implementation of a posterior urethral valves (PUV) clinic and standardized management pathway improves the short-term kidney outcomes of infants with PUV. METHODS: From 2016-2022, 50 consecutive patients were divided into groups after the implementation of the clinic (APUV, n = 29) and before (BPUV, n = 21) during a comparable timeframe. Assessed data included age at initial visit, timing and type of surgery, frequency of follow-up visits, medications, nadir creatinine, and development of CKD/kidney failure. Data are shown as median with interquartile range (IQR) and odds ratios (OR) with 95% confidence interval (CI). RESULTS: APUV had higher rates of prenatal diagnoses (12/29 vs. 1/21; p = 0.0037), earlier initial surgical intervention (8 days; IQR 0, 105 vs. 33 days; IQR 4, 603; p < 0.0001), and higher rates of primary diversions (10/29 vs. 0/21; p = 0.0028). Standardized management led to earlier initiation of alpha blockers (326 days; IQR 6, 860 vs. 991; IQR 149, 1634; p = 0.0019) and anticholinergics (57 days; IQR 3, 860 vs. 1283 days; IQR 477, 1718; p < 0.0001). Nadir creatinine was reached at earlier ages in APUV (105 days; IQR 2, 303 vs. 164 days; IQR 21, 447; p = 0.0192 BPUV). One patient progressed to CKD5 in APUV compared to CKD3, CKD5 and one transplant in BPUV. CONCLUSION: Implementing the PUV clinic with standardized treatment expedited postnatal management and resulted in a higher number of cases detected prenatally, a shift in primary treatment, younger ages at initial treatment, reduced time to nadir creatinine, and timely initiation of supportive medications. A higher resolution version of the Graphical abstract is available as Supplementary information.

Pre-versus postnatal presentation of posterior urethral valves: a multi-institutional experience.

OBJECTIVE: To compare the outcomes of pre- vs postnatally diagnosed posterior urethral valves (PUV) at two large paediatric centres in North America to ascertain if the prenatal diagnosis of PUV is associated with better outcomes. PATIENTS AND METHODS: All boys with PUV were identified at two large paediatric institutions in North America between 2000 and 2020 (The Hospital for Sick Children [SickKids, SK] and Children's Hospital of Philadelphia [CHOP]). Baseline characteristics and outcome measures were compared between those diagnosed pre- vs postnatally. Main outcomes of interest included progression of chronic kidney disease (CKD), the need for renal replacement therapy (RRT), and bladder function compromise, as determined by need for clean intermittent catheterisation (CIC). Time-to-event analyses were completed when possible. RESULTS: During the study period, 152 boys with PUV were treated at the SK (39% prenatal) and 216 were treated at the CHOP (71% prenatal). At the SK, there was no difference between the pre- and postnatal groups in the proportion of boys who required RRT, progressed to CKD Stage ≥3, or who were managed with CIC when comparing the timing of diagnosis. The time to event for RRT and CIC was significantly younger for prenatally detected PUV. At the CHOP, significantly more prenatal boys required RRT; however, there was no significant difference in the age this outcome was reached. The proportion of boys managed with CIC was not different but the time to event was significantly earlier in the prenatal group. CONCLUSION: This study represents the largest multi-institutional series of boys with PUV and failed to identify any difference in the outcomes of pre- vs postnatal detection of PUV. A multidisciplinary approach with standardisation of the treatment pathways will help in understanding the true impact of prenatal/early detection on outcomes of PUV.

Predicting childhood chronic kidney disease severity in infants with posterior urethral valve: a critical analysis of creatinine values in the first year of life.

BACKGROUND: Posterior urethral valve (PUV) is a leading cause of chronic kidney failure in children. Studies have shown that a creatinine nadir above historical cutoff values of 0.8 or 1.0 mg/dL correlates with worse kidney outcomes. The ability to use nadir creatinine more discriminately as a test of kidney outcomes is otherwise limited. METHODS: We performed a retrospective review of 102 infants treated with primary valve ablation prior to 1 year of age. Patient factors including creatinine at presentation (Cr-P), nadir within 6 weeks after ablation (Cr-6 W), and nadir within 1 year after ablation (Cr-1Y) were assessed as predictors of final chronic kidney disease (CKD) severity. An optimal threshold for four CKD levels was defined in incremental fashion using binary outcome with receiver operating characteristic (ROC). Multivariable logistic regression models compared Cr-P, Cr-6 W, and Cr-1Y while adjusting for patient factors. RESULTS: Boys were ablated at mean age of 36.3 days and followed for 6.6 years (± 3.7). When compared to other demographics, only creatinine remained independently predictive of CKD outcomes on multivariable analysis. ROC analysis demonstrated excellent diagnostic accuracy for Cr-6 W and Cr-1Y (p < 0.001) and acceptable accuracy for Cr-P (p < 0.005). Using the Cr-6 W and Cr-1Y models, high sensitivity and specificity creatinine nadir cutoffs were determined to predict each CKD outcome. CONCLUSIONS: The severity of childhood CKD can be predicted with high accuracy using the creatinine nadir within 6 weeks of ablation. The cutoff values described can be incorporated into a clinical setting for patient counseling and individual risk stratification.

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.

Correlation of Urinary Biomarkers (Interleukin-6, Transforming growth factor-ß, E-Cadherin, and MCP-1) with Conventional Parameters of Disease Progression in Patients of Posterior Urethral Valves: A Comparative Analysis.

Aims: Posterior urethral valves (PUV) are the leading cause of end-stage renal disease in boys. The study aimed to look at the ongoing renal damage and profibrotic activity by measuring the levels of Interleukin-6 (IL-6), Transforming growth factor-ß (TGF-ß), E-cadherin, and Monocyte Chemoattractant Protein-1 (MCP-1) and observing trends in subsequent follow-ups and at the same time correlating them with the established parameters of disease progression. Materials and Methods: This prospective study included 36 consecutive patients of PUV, managed over a period of 18 months. IL-6, TGF-ß, E-cadherin, and MCP-1 were measured in urine samples at the time of admission, pre-fulguration and 3 months' and 9 months' post fulguration. The observed values were correlated with the conventional parameters used in clinical practice. Results: All the biomarkers showed statistically significant trends when these values were compared on admission, postoptimization and 3 months' and 9 months' postfulguration. None of the biomarkers showed a significant correlation with renal function tests. E-Cadherin and TGF-ß showed a positive and a negative correlation with ultrasonography (USG) kidney, ureter, and bladder (KUB) respectively. E-Cadherin showed a positive correlation, whereas IL-6 and TGFß showed negative correlation respectively with micturating cystourethrogram (MCUG). IL-6 showed statistically a significant negative correlation with dimercapto succinic acid (DMSA). MCP-1 did not show any significant correlation with USG KUB, MCUG and DMSA. Conclusion: This study concludes that E-Cadherin, IL-6, TGF-ß can be promising urinary biomarkers for early detection of the ongoing renal damage in patients of PUV following valve fulguration. MCP-1 may have more complex interactions, with inflammatory markers; which warrants further research.

Is there a need for endoscopic evaluation in symptomatic boys with an unsuspicious urethra on VCUG? A consideration of secondary radiologic signs of posterior urethral valves.

INTRODUCTION: A significant proportion of PUV becomes symptomatic after the perinatal period. Voiding cystourethrography (VCUG) often fails to identify PUVs. This study evaluates the relationship between the radiological appearance of the posterior urethra, potential secondary radiological signs and endoscopically documented PUV in boys with febrile UTIs, VUR, refractory symptoms of bladder overactivity or suggestive sonography findings. PATIENTS AND METHODS: Data on VCUG findings and endoscopy from 92 boys (mean age 27 months) who underwent endoscopic PUV incision between 2012 and 2017 following a VCUG were reviewed. 24 boys with endoscopically unsuspicious urethras were included as control group (mean age 27.5 months). Statistical analysis was performed using Fisher's exact test. RESULTS: In patients with PUV, the urethra was suspicious on a preoperative VCUG in 45.7%, whereas it appeared normal in 54.3%. Abortive forms of PUV were more frequently found in patients with a radiologically unsuspicious urethra (30%vs.16.7%, p = 0.15). Bladder neck hypertrophy on VCUG (16.7%vs.60.9%, OR 7.5, p < 0.001), a trabeculated bladder on VCUG (72%vs.37.5%, OR 4.3, p < 0.001) and a hypertrophied musculus interuretericus (38%vs.4.2%, OR 11.7, p < 0.001) were more common in patients with PUV and urethras appearing normal on VCUG as compared to controls. CONCLUSION: Unsuspicious findings of the urethra on VCUG cannot exclude a relevant PUV and implicate a risk of disregarding abortive forms. The presence of secondary radiologic signs of infravesical obstruction on a VCUG despite an unsuspicious posterior urethra in boys with recurrent UTI's as well as refractory symptoms of bladder overactivity or suggestive signs on sonography must be further clarified endoscopically.

Z-scores of fetal bladder size for antenatal differential diagnosis between posterior urethral valves and urethral atresia.

OBJECTIVE: To construct reference values for fetal urinary bladder distension in pregnancy and use Z-scores as a diagnostic tool to differentiate posterior urethral valves (PUV) from urethral atresia (UA). METHODS: This was a prospective cross-sectional study in healthy singleton pregnancies aimed at constructing nomograms of fetal urinary bladder diameter and volume between 15 and 35 weeks' gestation. Z-scores of longitudinal bladder diameter (LBD) were calculated and validated in a cohort of fetuses with megacystis with ascertained postnatal or postmortem diagnosis, collected from a retrospective, multicenter study. Correlations between anatomopathological findings, based on medical examination of the infant or postmortem examination, and fetal megacystis were established. The accuracy of the Z-scores was evaluated by receiver-operating-characteristics (ROC)-curve analysis. RESULTS: Nomograms of fetal urinary bladder diameter and volume were produced from three-dimensional ultrasound volumes in 225 pregnant women between 15 and 35 weeks of gestation. A total of 1238 urinary bladder measurements were obtained. Z-scores, derived from the fetal nomograms, were calculated in 106 cases with suspected lower urinary tract obstruction (LUTO), including 76 (72%) cases with PUV, 22 (21%) cases with UA, four (4%) cases with urethral stenosis and four (4%) cases with megacystis-microcolon-intestinal hypoperistalsis syndrome. Fetuses with PUV showed a significantly lower LBD Z-score compared to those with UA (3.95 vs 8.83, P < 0.01). On ROC-curve analysis, we identified 5.2 as the optimal Z-score cut-off to differentiate fetuses with PUV from the rest of the study population (area under the curve, 0.84 (95% CI, 0.748-0.936); P < 0.01; sensitivity, 74%; specificity, 86%). CONCLUSIONS: Z-scores of LBD can distinguish reliably fetuses with LUTO caused by PUV from those with other subtypes of LUTO, with an optimal cut-off of 5.2. This information should be useful for prenatal counseling and management of LUTO. © 2021 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Evaluation of polyuria and polydipsia along with other established prognostic factors in posterior urethral valves for progression to kidney failure: experience from a developing country.

BACKGROUND: Up to 50% of children with posterior urethral valves (PUV) progress to kidney failure. This study aimed to evaluate polyuria and polydipsia and other established variables with later development of kidney failure in children with PUV. METHODS: Retrospective analysis of 297 children with PUV who underwent ablation of valves between January 1992 and January 2015 at our tertiary care center. Patients were divided into two groups: those who developed kidney failure (group 1) and those who did not (group 2). Specific prognostic factors for progression to kidney failure were analyzed including age at presentation < 1 year, nadir serum creatinine > 1.0 mg/dl, bilateral grade 3 or higher VUR at diagnosis, recurrent febrile UTIs, severe bladder dysfunction, polyuria, and polydipsia. RESULTS: Thirty-eight (12.8%) patients progressed to kidney failure. Twenty-four and 64 patients were polyuric in group 1 and group 2 respectively (p < 0.001, Z-4.4666). Twenty-two and 61 patients were polydipsic in both groups respectively (p < 0.001). On univariate analysis, predicting variables were as follows: age at presentation < 1 year (p < 0.001), nadir serum creatinine > 1 mg/dl (p < 0.001), B/L high-grade VUR (p < 0.001), severe bladder dysfunction (p < 0.001), recurrent febrile UTIs (p = 0.002), polyuria (p < 0.001), and polydipsia (p < 0.001). On multivariate Cox regression analysis, severe bladder dysfunction, recurrent febrile UTIs, polyuria, and polydipsia were identified as significant prognostic factors predictive of ultimate progression to kidney failure. CONCLUSION: Polyuria and polydipsia along with recurrent febrile UTI and bladder dysfunction are major prognostic factors affecting long-term kidney outcome in cases of PUV. Graphical abstract.

Urethroplasty with balloon catheterization in fetal lower urinary tract obstruction: observational study of 10 fetuses.

OBJECTIVE: To present the preliminary outcomes of fetal urethroplasty using a coronary angioplasty balloon catheter in lower urinary tract obstruction (LUTO). METHODS: We included 10 consecutive male fetuses diagnosed with LUTO caused by presumed isolated posterior urethral valves (PUVs), who underwent urethroplasty with a balloon catheter in our center between 2015 and 2018. During urethroplasty, the fetal urethra was dilated using a balloon catheter (diameter, 0.014 inches; balloon size, 2 × 9 mm) inserted under ultrasonographic guidance via an 18-gauge needle introduced into the fetal bladder. RESULTS: Mean gestational age at the time of urethroplasty was 17.8 (range, 16.5-20.4) weeks. All fetuses survived the procedure without any complications and there was no case of preterm prelabor rupture of the membranes. The procedure was successful in 5/10 (50%) fetuses, while in the other five (50%), we were unable to insert the balloon catheter into the urethra. In the five successfully treated cases, mean gestational age at delivery was 38 (range, 36-40) weeks and presence of PUVs was confirmed after birth. All five neonates micturated spontaneously and presented with normal urine output after birth. During the follow-up period, the parameters of kidney function were within normal limits in two neonates, whereas signs of impaired renal function were seen in another two. The other was diagnosed with renal insufficiency and required kidney transplant with bladder sparing at 2 years of age. CONCLUSIONS: Urethroplasty with a balloon catheter is a new prenatal treatment option for fetuses with PUVs. By restoring fetal micturition, the procedure can preserve normal urinary bladder and kidney function. Although data on its efficacy and potential to differentiate the etiology of LUTO are sparse, a significant advantage of this method is its safety for the fetus and the mother. Even if the neonates develop renal insufficiency, they may be eligible for kidney transplant with connection to their own bladder, without the need for urostomy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Comparative outcome analysis of pediatric kidney transplant in posterior urethral valves children with or without pretransplant Mitrofanoff procedure.

BACKGROUND: Urinary diversion using catheterizable channel among posterior urethral valve (PUV) patients may help to alleviate the functional concerns of the bladder on the allograft. Herein, we review our series of PUV patients undergoing renal transplants at a single institution to determine outcomes between those with and without pretransplant Mitrofanoff. METHODS: PUV cases in our transplant database from 2000 to 2017 were identified. Data collected included clinical demographics, presentation of PUV, bladder function, implementation of dialysis and donor type. Post-transplant variables included graft function, and bladder function including incontinence and UTI development. Comparison between with vs without pretransplant Mitrofanoff patient groups was performed using Fisher's exact and t test analysis. RESULTS: Overall, 22 cases were analyzed. The majority (77%) had a prenatal diagnosis of PUV, and 23% had a symptomatic presentation. Pretransplant Mitrofanoffs were performed in 40.9% of cases. The overall age at transplant was 10 ± 5 years. Five percent experienced post-transplant incontinence and 23% UTIs. No difference between groups was noted in variables including age at transplant, the timing of PUV diagnosis. Mitrofanoff group patients had more symptomatic febrile UTIs than those without Mitrofanoff (67% vs 15%; P = .03); however, there was no difference in post-transplant UTI development. Furthermore, the Mitrofanoff group seems to have later onset of dialysis or need for transplant (age at the start of dialysis 36 ± 56 vs 156 ± 25 months, P < .001). CONCLUSION: Our study suggests that patients with early PUV diagnoses who develop symptomatic UTI may benefit from early creation of a Mitrofanoff cathetherizable channel, which is associated with delayed ESRD progression and need for dialysis.

Clinical predictors of chronic kidney disease in congenital lower urinary tract obstruction.

Congenital lower urinary tract obstruction is associated with oligohydramnios and significant perinatal mortality and long-term chronic kidney disease. The counseling of families facing this diagnosis, especially when prenatal intervention is proposed, is fraught with ambiguity. This review aims to equip the provider with the current evidence behind the conventional and novel biomarkers predictive of chronic kidney disease. The relevant clinical predictors are categorized by when they are identified, antenatally or postnatally, and as either anatomic or chemical. They are considered for their prognostic value and the challenges in obtaining them, specifically the risk to the fetus in the case of prenatal biomarkers. Serum creatinine in infancy is the traditional chemical biomarker of kidney function and continues to be a consistent predictor of future serum creatinine. ß-2 microglobulin may provide earlier information regarding fetal glomerular and tubular function and is also predictive of long-term serum creatinine. Renal parenchymal area is an anatomic surrogate of nephron mass that is used in both prenatal and postnatal settings. Understanding the anatomic and chemical biomarkers is essential for future refinement of the staging algorithm used to distinguish which patients may benefit from early in utero intervention.

Long-term outcome of kidney transplantation in patients with congenital anomalies of the kidney and urinary tract.

BACKGROUND: Congenital anomalies of the kidney and urinary tract (CAKUT) are a leading cause of end-stage kidney failure in the young. However, there is limited information on long-term outcomes after kidney transplantation in this group. We explored the outcomes of kidney transplant in patients with the 3 most common severe forms of CAKUT: posterior urethral valves (PUV), reflux nephropathy and renal hypoplasia/dysplasia. METHODS: Data were extracted from the Australian & New Zealand Dialysis & Transplant Registry on first kidney transplants performed between 1985 and 2015 in recipients with a primary diagnosis of PUV, renal hypoplasia/dysplasia or reflux nephropathy (under the age of 30 years). Using multivariate Cox regression, we compared death-censored graft survival between the three groups. RESULTS: One hundred twenty-seven patients with PUV, 245 with hypoplasia/dysplasia and 727 with reflux nephropathy were included. A 10-year graft survival in PUV, hypoplasia/dysplasia and reflux nephropathy was 70%, 76% and 70%, respectively and a 20-year graft survival was 30%, 53% and 49%. After adjusting for age at transplant, graft source and HLA matching, there was evidence for poorer graft survival in PUV (HR, 1.65; 95% CI, 1.15 to 2.38). CONCLUSIONS: Graft survival of the first transplant in CAKUT is favourable at 10 years; however, recipients with PUV have increased risk of graft loss beyond a 10-year post-transplant, which may be related to bladder dysfunction.

Voiding cystography: an unusual route of induced hypothyroidism by iodine overdose in two newborns with chronic kidney disease.

BACKGROUND: Iatrogenic induced hypothyroidism had been described in newborns and more particularly in preterm infants after cutaneous or intravenous exposure to iodine. CASE-DIAGNOSIS : We reported a new risk of iodine intoxication with the cases of two newborns who developed hypothyroidism after intra vesical iodine injection during a cystography, which was performed to confirm antenatal diagnosis of posterior urethral valves (PUV). The newborns both developed transient hypothyroidism due to an iodine overdose. CONCLUSIONS: These two observations suggest that voiding cystourethrography (VCUG) should be carefully considered in newborns with severe uropathy, particularly in the case of renal insufficiency. If indicated, thyroid function should be monitored in the following weeks, and in case of hypothyroidism treatment should be started.

A clinical predictive model of chronic kidney disease in children with posterior urethral valves.

BACKGROUND: Posterior urethral valves (PUVs) are associated with severe consequences to the urinary tract and are a common cause of chronic kidney disease (CKD). The aim of this study was to develop clinical predictive model of CKD in a cohort of patients with PUVs. METHODS: In this retrospective cohort study, 173 patients with PUVs were systematically followed up at a single tertiary unit. The primary endpoint was CKD ≥ stage 3. Survival analyses were performed by Cox regression proportional hazard models with time-fixed and time-dependent covariables. RESULTS: Mean follow-up time was 83 months (SD, 70 months). Sixty-five children (37.6%) developed CKD stage ≥ 3. After adjustment by the time-dependent Cox model, baseline creatinine, nadir creatinine, hypertension, and proteinuria remained as predictors of the endpoint. After adjustment by time-fixed model, three variables were predictors of CKD ≥ stage 3: baseline creatinine, nadir creatinine, and proteinuria. The prognostic risk score was divided into three categories: low-risk (69 children, 39.9%), medium-risk (45, 26%), and high-risk (59, 34.1%). The probability of CKD ≥ stage 3 at 10 years age was estimated as 6%, 40%, and 70% for patients assigned to the low-risk, medium-risk, and high-risk groups, respectively (P < 0.001). The main limitation was the preclusion of some relevant variables, especially bladder dysfunction, that might contribute to a more accurate prediction of renal outcome. CONCLUSION: The model accurately predicts the risk of CKD in PUVs patients. This model could be clinically useful in applying timely intervention and in preventing the impairment of renal function.

Antenatal Workup of Early Megacystis and Selection of Candidates for Fetal Therapy.

OBJECTIVE: To investigate the best criteria for discriminating fetuses with isolated posterior urethral valves from those theoretically not eligible for fetal treatment because of complex megacystis, high chance of spontaneous resolution, and urethral atresia. METHODS: A retrospective national study was conducted in fetuses with megacystis detected before 17 weeks' gestation (early megacystis). RESULTS: In total, 142 cases with fetal megacystis were included in the study: 52 with lower urinary tract obstruction, 29 with normal micturition at birth, and 61 with miscellaneous syndromal associations, chromosomal and multiple structural abnormalities (complex megacystis). Only a nuchal translucency > 95th centile, and not a longitudinal bladder diameter ≤15 mm (p = 0.24), significantly increased the risk of complex megacystis (p < 0.01). Cases with a high chance of spontaneous resolution were identified by using the cut-off of 12 mm, as demonstrated in a previous study, and the finding of an associated umbilical cord cyst carried a high-risk of urethral atresia (odds ratio: 15; p = 0.026), an unfavorable condition for antenatal treatment. An algorithm encompassing these three criteria demonstrated good accuracy in selecting fetuses theoretically eligible for fetal treatment (specificity 73%; sensitivity 92%). CONCLUSIONS: Cases theoretically eligible for early fetal therapy are those with normal nuchal translucency, a longitudinal bladder diameter > 12 mm, and without ultrasound evidence of umbilical cord cysts.

Consensus on the Management of Posterior Urethral Valves from Antenatal Period to Puberty.

The need for successful management of posterior urethral valves always captivates the minds of pediatric surgeons. Its success, however, depends on several factors ranging from prenatal preservation of upper tracts to postoperative pharmacological compliance. Regardless of measures available, some cases do not respond and progress to end stage. The management depends on several issues ranging from age and severity at presentation to long-term follow-up and prevention of secondary renal damage and managing valve bladder syndrome. This article is based on a consensus to the set of questionnaires, prepared by research section of Indian Association of Paediatric Surgeons and discussed by experienced pediatric surgeons based in different institutions in the country. Standard operating procedures for conducting a voiding cystourethrogram and cystoscopy were formulated. Age-wise contrast dosage was calculated for ready reference. Current evidence from literature was also reviewed and included to complete the topic.

Current strategies to predict and manage sequelae of posterior urethral valves in children.

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.

Predicting and Modifying Risk for Development of Renal Failure in Boys with Posterior Urethral Valves.

PURPOSE OF REVIEW: The purpose of this review is to bring the reader up to date on the current risk factors for the development of renal deterioration in the boys with posterior urethral valves (PUV) and approaches to modify this risk. RECENT FINDINGS: Renal bladder ultrasound (RBUS) is routinely performed in boys with PUV and recent advancements allow imaging processing that can more accurately quantify renal parenchyma and correlate this with risk for renal loss. Refinement of urine studies may improve our ability to stratify patients into renal loss categories. Use of videourodynamics (VUDS) allows refined assessment of the valve bladder to identify those who might benefit from secondary procedures and/or the addition of targeted pharmacotherapy to improve bladder emptying or dangerous storage pressures. All boys with a history of PUV are at a significant long-term risk of renal deterioration. The literature suggests that several technical advances have improved our ability to predict this risk, although there needs to be further refinement and validation before widespread use. Utilization of close follow-up, VUDS, pharmacotherapy, and bladder drainage provide the best methods to improve care to this group of patients and if more studies confirm their utility, adoption of these as part of standard of care protocols may be warranted.