Posterior Urethral Valves (PUV) – from prenatal ultrasound features to postnatal outcomes

• Applicant: Dr. Franziska Juliane Richter
• Subject Area: Reproductive Medicine, Urology
• Term: from 2023 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 518327802

• Final Report Year: 2024

Final Report Abstract

Lower urinary tract obstruction (LUTO) affects 2-3 in 10000 male births and is associated with high mortality rates of up to 30% as well as severe comorbidities such as pulmonary hypoplasia, bladder dysfunction and chronic kidney disease (CKD) with one third progressing to end-stage renal disease (ESRD), irrespective of the underlying condition. The most common underlying reason for LUTO that occurs in 1-2 in 10.000 male births is posterior urethral valves (PUV) as a result of incomplete incorporation of the Wolffian duct, followed by urethral atresia and urethral stenosis or stricture. Early prenatal detection of LUTO, especially during the first trimester of pregnancy, is associated with a poor prognosis of these fetuses. In the presence of typical ultrasound features, such as megacystis, hydronephrosis and the keyhole sign, the prenatal diagnosis of LUTO is very obvious. However, a differentiation of underlying reasons for LUTO or an exact risk stratification of postnatal outcomes and the likelihood of a potentially poor prognosis of the fetus isn’t possible solely based on these ultrasound features and prenatal detection rates in the literature vary between 33-62%. Although historical data of our detection rates were at the upper end of this span, they are still suboptimal. This uncertainty represents a major challenge for providers and can overwhelm parents. Confronted with rather abstract clinical parameters and assumptions on a low level of evidence that might not even apply to their case, parents try to grasp the meaning of these parameters and understand the consequences for their future life’s which results in nearly half of these families opting to terminate the pregnancy, eventually. Given these challenges, we were wondering if prenatal counselling can be further improved by a more personalized approach using risk stratification based on ultrasound features of individual patients that predicts outcomes like postnatal dialysis, transplantation or death in LUTO fetuses in order to support parents in the process of decision making about the LUTO pregnancy. Therefore, we built a prenatal LUTO database in collaboration with a tertiary fetal center and matched these cases to the pre-existing postnatal database at our tertiary children’s center. Based on these data, we used prenatal ultrasounds of continued LUTO pregnancies to build a random forest model that predicts the most important postnatal outcomes dialysis, transplantation and death. The model built from this training set was tested using ultrasounds of terminated pregnancies with a confirmed LUTO diagnosis for internal validation. The first results are reassuring and demonstrate that it is possible to predict postnatal outcomes in LUTO fetuses based on prenatal ultrasound findings with reasonable accuracy, which can be a useful tool to improve prenatal counseling and decision making based on more personalized risk stratifications. This supportive tool represents an opportunity to enhance prenatal care of LUTO fetuses in terms of early and more proactive management.

Publications

• P015: Posterior Urethral Valves (PUV) and Anterior Urethral Valves (AUV) with and without concomitant PUV: Matched cohort study at a high-risk pediatric
  Richter J., Dos Santos J., Sánchez C., Moreno Bencardino C., Chua M.E., Kim J.K., Khondker A., Lorenzo A.J. & Rickard M.
  
• Comparison of outcomes of prenatal versus postnatal presentation of posterior urethral valves: a systematic review and meta-analysis. World Journal of Urology, 40(9), 2181-2194.
  Yadav, Priyank; Rickard, Mandy; Kim, Jin Kyu; Richter, Juliane; Lolas, Marisol; Alshammari, Dheidan; Chua, Michael E.; Dos Santos, Joana & Lorenzo, Armando J.
  
• Predicting the Future of Patients with Obstructive Uropathy—A Comprehensive Review. Current Pediatrics Reports, 10(4), 202-213.
  Richter, Juliane; Rickard, Mandy; Kim, Jin Kyu; Erdman, Lauren; Lorenzo, Armando J. & Chua, Michael
  
• The impact of standardized postnatal treatment and implementation of the PUV-clinic on postnatal outcome: a retrospective single-center cohort study. Society for Pediatric Urology (SPU) Fall congress 2022 (oral presentation)
  Richter J., Natasha Brownrigg, Joana Dos Santos, Justin Kim, Michael Chua, Armando J. Lorenzo & Mandy Rickard
  
• Ureterostomies for Management of PUV Patients: A Case Series of 8 Patients. Society for Pediatric Urology (SPU) Fall congress 2022 (oral presentation)
  Richter J., Rickard M., Kim J.K., Chua M.E. & Lorenzo A.J.
  
• 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?. Urology, 179, 151-157.
  Kim, Jin K.; Khondker, Adree; Chua, Michael E.; Alshammari, Dheidan; Richter, Juliane; Dos Santos, Joana; Brownrigg, Natasha; D.’Souza, Neeta; Weaver, John; Tasian, Gregory; Lorenzo, Armando J. & Rickard, Mandy
  
• Does early postoperative Doppler ultrasound differentiate acute tubular necrosis vs. rejection after pediatric renal transplantation? European society for pediatric urology (ESPU) congress 2023 (oral presentation)
  Yadav P., Santos J.D., Rickard M., Alshammari D., Khondker A., Richter J., Kim J.K., Teoh C.W., Lorenzo A.J. & Chua M.E.
  
• Does the presence of pressure “Pop-Offs” impact voiding efficiency and bladder outcomes in posterior urethral valves? European society for pediatric urology (ESPU) congress 2023 (oral presentation)
  Khondker A., Yadav P., Kim J.K., Chua M.E., Brownrigg N., Richter J., Santos J.D., Lorenzo A.J. & Rickard M.
  
• Does VURD syndrome impact voiding efficiency in posterior urethral valves?. Journal of Pediatric Urology, 19(4), 424.e1-424.e7.
  Khondker, Adree; Yadav, Priyank; Kim, Jin K.; Chua, Michael E.; Brownrigg, Natasha; Richter, Juliane; Dos Santos, Joana; Lorenzo, Armando J. & Rickard, Mandy
  
• Implementation of a standardized clinical pathway in a dedicated posterior urethral valves clinic: short-term outcomes. Pediatric Nephrology, 38(11), 3735-3744.
  Rickard, Mandy; Lorenzo, Armando J.; Richter, Juliane; Brownrigg, Natasha; Kim, Jin K.; Chua, Michael; Goraya, Noreen; Khondker, Adree; Yadav, Priyank; Keefe, Daniel T.; Shinar, Shiri & Dos Santos, Joana
  
• It’s not too late: Secondary diversion after failed ablation does not commit patients with lower urinary tract obstruction (LUTO) to worse short-term outcomes. American Academy of Pediatrics (AAP) congress 2023 (oral presentation).
  Richter J., Rickard M., Santos J.D., Chua M.E. & Lorenzo A.J.
  
• It’s not too late: Secondary diversion after failed ablation does not commit patients with lower urinary tract obstruction (LUTO) to worse short-term outcomes. American Academy of Pediatrics (AAP) congress 2023 (oral presentation).
  Richter J., Rickard M., Santos J.D., Chua M.E. & Lorenzo A.J.
  
• Kidney function and transplants in prune belly syndrome: a scoping review. Pediatric Nephrology, 39(4), 1053-1063.
  Khondker, Adree; Ahmad, Ihtisham; Kim, Kellie; Malik, Shamir; Kim, Jin K.; Chua, Michael; Richter, Juliane; Chan, Justin YH; Baker, Linda A.; Lorenzo, Armando J. & Rickard, Mandy
  
• Pathological Findings in fetuses terminated for suspected LUTO diagnosis – experience from a high-risk fetal center. European society for pediatric urology (ESPU) congress 2023 & DGU 2023. (oral presentation) and International Society for Prenatal Diagnosis (ISPD) 2023 (poster presentation)
  Richter J., Good H., Kim J.K., Shannon P., Santos, J.D., Brownrigg N., Chua M.E., Lorenzo A.J., Rickard M., Van Mieghem T. & Shinar S.
  
• Posterior urethral valves, pressure pop-offs, and kidney function: systematic review and meta-analysis. World Journal of Urology, 41(7), 1803-1811.
  Khondker, Adree; Kim, Kellie; Najafabadi, Borna Tadayon; Nguyen, David-Dan; Kim, Jin Kyu; Yadav, Priyank; Brownrigg, Natasha; Richter, Juliane; E., Chua Michael; Dos Santos, Joana; Rickard, Mandy & Lorenzo, Armando J.
  
• Postoperative fluid collections after pediatric renal transplantation: Natural history, and progression to symptomatic lymphocele. European society for pediatric urology (ESPU) congress 2023 (oral presentation)
  Yadav P., Rickard M., Alshammari D., Teoh C.W., Khondker A., Richter J., Kim J.K., Santos J.D., Chua M.E. & Lorenzo A.J.
  
• Safety and tolerability of super selective alpha-1 adrenergic blockers in children under the age of 3 years: Prospective experience in patients with posterior urethral valves (PUV). American Academy of Pediatrics (AAP) congress 2023 and German association of urology (DGU) congress 2023 (oral presentation).
  Richter J., Rickard M., Chua M.E., Kim J.K., Brownrigg N., Khondker A., Lorenzo A.J. & Santos J.D.
  
• Safety and tolerability of super selective alpha-1 adrenergic blockers in children under the age of 3 years: Prospective experience in patients with posterior urethral valves (PUV). American Academy of Pediatrics (AAP) congress 2023 and German association of urology (DGU) congress 2023 (oral presentation).
  Richter J., Rickard M., Chua M.E., Kim J.K., Brownrigg N., Khondker A., Lorenzo A.J. & Santos J.D.
  
• The effect of primary urinary diversion on kidney function in posterior urethral valve: A matched comparison. Urology, 172, 170-173.
  Khondker, Adree; Kim, Jin K.; Chua, Michael E.; Kwong, Jethro C.C.; Chan, Justin Y.H.; Yadav, Priyank; Richter, Juliane; Dos Santos, Joana; Brownrigg, Natasha; Lorenzo, Armando J. & Rickard, Mandy
  
• The implications of decreased renal reserve: A multi-institutional evaluation of solitary functioning kidneys in posterior urethral valves. European society for pediatric urology (ESPU) congress 2023 (oral presentation)
  Kim J.K., Chua M.E., Lorenzo A.J., Santos J.D., Richter J., Yadav P., Khondker A., Paraboschi I., Giannettoni A., Mishra P., Clothier J., Rickard M. & Garriboli M.
  
• The incidence of urinary tract infections among infants with isolated hydronephrosis: an epidemiological evaluation of time-varying exposure analysis. European society for pediatric urology (ESPU) congress 2023 (oral presentation)
  Kim J.K., Chancy M., Chua M.E., Brownrigg N., Santos J.D., Richter J., Van Mieghem T., Lorenzo A.J. & Rickard M.
  
• The role of circumcision in preventing urinary tract infections in children with antenatal hydronephrosis: Systematic review and meta-analysis. Journal of Pediatric Urology, 19(6), 766-777.
  Chan, Justin YH.; Khondker, Adree; Lee, Min Joon; Kim, Jin Kyu; Chancy, Margarita; Chua, Michael E.; Dos Santos, Joana; Brownrigg, Natasha; Richter, Juliane; Lorenzo, Armando J. & Rickard, Mandy
  
• Time-varying exposure analysis of infants with isolated hydronephrosis: an epidemiological study. American Academy of Pediatrics (AAP) congress 2023 (oral presentation).
  Kim J.K., Chancy M., Chua M.E., Brownrigg N., Dos Santos J., Richter J., Van Mieghem T., Lorenzo A.J. & Rickard M.
  
• Trends in management of fetuses with suspected lower urinary tract obstruction (LUTO) – a high risk fetal and pediatric center experience in a universal access to care system. European Paediatric Surgeons' Association (EUPSA) Congress 2023 (oral presentation)
  Richter J., Shinar S., Good H., Doktor F., Kim J.K., Santos, J.D., Brownrigg Chua M.E., Lorenzo A.J., Rickard M. & Van Mieghem T.
  
• Trends in Management of Fetuses with Suspected Lower Urinary Tract Obstruction (LUTO): A High-Risk Fetal and Pediatric Center Experience in a Universal-Access-to-Care System. European Journal of Pediatric Surgery, 34(01), 091-096.
  Richter, Juliane; Doktor, Fabian; Good, Hayley; Erdman, Lauren; Kim, Jin K.; Santos, Joana Dos; Brownrigg, Natasha; Chua, Michael; Lorenzo, Armando J.; Rickard, Mandy; Van Mieghem, Tim & Shinar, Shiri
  
• What are the (un)intended consequences of overturning Roe vs. Wade? A Canadian perspective on elective termination of pregnancies in cases of lower urinary tract obstruction (LUTO). European society for pediatric urology (ESPU) congress 2023. (oral presentation)
  Rickard M., Richter J., Santos J.D., Brownrigg N., Lorenzo A.J., Van Mieghem T. & Shinar S.
  
• What If They Continued The Pregnancy? Using Prenatal Ultrasound Findings to Predict Postnatal Outcomes for Fetuses with Lower Urinary Tract Obstruction (LUTO) To Improve Counseling and Aid in Decision Making. European society for pediatric urology (ESPU) congress 2023, European Association of Urology (EAU) congress 2023 & DGU 2023 (oral presentation), International Society for Prenatal Diagnosis (ISPD) 2023 & 49th Annual Gallie Day of the University of Toronto Department of Surgery (poster presentation)
  Richter J., Shinar S., Erdman E., Good H., Kim J.K., Santos, J.D., Brownrigg N., Khondker A., Yadav P., Chua M.E., Van Mieghem T., Rickard M. & Lorenzo A.J.
  
• A0116: Early prenatal detection of LUTO is associated with increased risk of kidney transplantation - a multi-institutional trans-atlantic experience. European Association of Urology (EAU) congress 2024 (oral presentation)
  Richter J., Harper L., Pecorelli S., Good H., Dos Santos J., Shinar S., Van Mieghem T., Lorenzo A.J. & Rickard M.
  
• Assessing safety and tolerability of super selective alpha-1 adrenergic blockers in infants under 3 years: Insights from a single-center study on lower urinary tract obstruction (LUTO). Journal of Pediatric Urology, 20, S35-S42.
  Richter, Juliane; Rickard, Mandy; Chua, Michael; Kim, Jin K.; Chancy, Margarita; Brownrigg, Natasha; Khondker, Adree; Lorenzo, Armando J. & Dos Santos, Joana
  
• External validation and reliability assessment of posterior urethral morphology on initial voiding cystourethrogram as a predictor for infants with posterior urethral valves. Journal of Pediatric Urology, 20(2), 253.e1-253.e6.
  Khondker, Adree; Chelliahpillai, Yashan; Machado, Mikayla; Kaab, Amine; Richter, Juliane; Kim, Jin Kyu; Chua, Michael; Dos Santos, Joana; Rickard, Mandy & Lorenzo, Armando J.
  
• Isolated Posterior Urethral Valves and Anterior Urethral Valves With and Without Concomitant PUV: Matched Cohort Study at a High-risk Pediatric Center. Urology, 194, 196-202.
  Richter, Juliane; Dos Santos, Joana; Sánchez, Catalina; Bencardino, Camila Moreno; Chua, Michael E.; Kim, Jin K.; Khondker, Adree; Lorenzo, Armando J. & Rickard, Mandy
  
• Obesity in pediatric kidney transplant patients is not associated with higher risk of postoperative complications – a 10-year single center experience. European society for pediatric urology (ESPU) congress 2024 (oral presentation)
  Richter J., Doktor F., Rickard M., Dos Santos J., Chua M.E., Teoh C.W., Yadav P., Kim J.K. & Lorenzo A.J.
  
• P013: Revisiting the vascular hitch procedure for crossing vessels in paediatric patients – a longitudinal institutional experience over 15 years. European Association of Urology (EAU) congress 2024 (oral presentation)
  Richter J., Dos Santos J., Sánchez C., Moreno Bernardino C., Romao R., Keefe D.T., Chua M.E., Rickard M. & Lorenzo A.J.
  
• Pathological Findings in Fetuses Terminated for Suspected Lower Urinary Tract Obstruction: Experience From a High-Risk Fetal Center in Canada. Journal of Urology, 211(2), 305-312.
  Richter, Juliane; Rickard, Mandy; Good, Hayley; Kim, Jin K.; Shannon, Patrick; Dos, Santos Joana; Chua, Michael E.; Lorenzo, Armando J.; Van Mieghem, Tim & Shinar, Shiri
  
• S19-2: “Atypical presentation of Lower Urinary Tract Obstruction: A case for heightened level of suspicion and use of the Toronto Nomogram”. European society for pediatric urology (ESPU) congress 2024 (oral presentation)
  Richter J., Good H., Chua M.E., Kim J.K., Dos Santos J., Lorenzo A.J., Van Mieghem T., Shinar S. & Rickard M.