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We thank Thomas Kohl for his correspondence on our ERKNet Consensus Statement on prenatal LUTO (Capone, V. et al. Definition, diagnosis and management of fetal lower urinary tract obstruction: consensus of the ERKNet CAKUT-Obstructive Uropathy Work Group. Nat. Rev. Urol. 19, 295–303 (2022)1), which raises some important issues (Kohl, T. Management of very young fetuses with LUTO. Nat. Rev. Urol. https://doi.org/10.1038/s41585-022-00636-8 (2022)2). In our paper, we recommend offering prenatal intervention in fetuses with LUTO, as this approach increases perinatal survival (defined as survival at 6 months of age) compared with conservative management (57% versus 39%, respectively), with no evidence of effects on long-term mortality and kidney function. This recommendation is based on published literature reporting intrauterine treatment by vesico-amniotic shunt (VAS) placement at 20–27 weeks of gestational age in most studies1. We are aware of the importance of early treatment in the most severe instances, with the objective to improve kidney function. However, no sufficient evidence is available to make a recommendation on the optimal timing of prenatal intervention.
The study by Kohl and colleagues involves 28 fetuses with severe megacystis treated before 16 weeks’ gestation3. In this study, very early treatment is associated with fetal loss in 9 of 28 instances (32%), with 4 demises after intervention and 5 terminations of pregnancy. Moreover, a high rate of post-natal complications is observed in survivors, including bowel atresia, vesico-cutaneous fistulas and bowel eventration.
Prenatal guidelines on invasive diagnostic testing recommend not to perform amniocentesis, which is carried out with a thinner needle than the devices used for VAS, before 15 weeks’ gestation, owing to the high rate of chorioamniotic membrane separation and consequent rupture of membranes (grade A recommendation)4. Thus, further research should be carried out to investigate the safety and efficacy of VAS before 16 weeks, regardless of the device used.
The authors also report a normal kidney function in 15 of 19 survivors (79%). However, this evidence only refers to short-term kidney function based on serum creatinine at discharge from hospital, which is insufficient to define the long-term potential need of kidney replacement therapy for these children, as also underlined in a commentary article5. In a future consensus paper, finding an agreement on a common way to assess postnatal kidney function in children who underwent prenatal treatment, both in terms of age of follow-up visits and type of assessment will be crucial.
In conclusion, on the basis of current evidence, no recommendation can be made on very early prenatal treatment of LUTO, considering the high proportion of fetal demise and postnatal complications related to the procedure. Based on Kohl’s data and suggestions, we support the need for large studies in which early treatment of megacystis is assessed under strict protocols to clarify the safety of these early procedures. Additionally, we also encourage long follow-up monitoring to assess the potential benefits of early intervention on kidney function preservation.
ReferencesCapone, V. et al. Definition, diagnosis and management of fetal lower urinary tract obstruction: consensus of the ERKNet CAKUT-Obstructive Uropathy Work Group. Nat. Rev. Urol. 19, 295–303 (2022).
Kohl, T. Management of very young fetuses with LUTO. Nat. Rev. Urol. https://doi.org/10.1038/s41585-022-00636-8 (2022).
Kohl, T., Fimmers, R., Axt-Fliedner, R., Degenhardt, J. & Brückmann, M. Vesico-amniotic shunt insertion prior to the completion of 16 weeks results in improved preservation of renal function in surviving fetuses with isolated severe lower urinary tract obstruction (LUTO). J. Pediatr. Urol. 18, 116–126 (2022).
Ghi, T. et al. ISUOG practice guidelines: invasive procedures for prenatal diagnosis. Ultrasound Obstet. Gynecol. 48, 256–268 (2016).
Farrugia, M.-K. Vesico-amniotic shunt insertion prior to the completion of 16 weeks results in improved preservation of renal function in surviving fetuses with isolated severe lower urinary tract obstruction (LUTO). J Pediatr. Urol. 18, 129–130 (2022).
Author informationAuthors and AffiliationsPediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca’ Granda-Ospedale Maggiore Policlinico, Milan, Italy
Valentina Capone & Giovanni Montini
Fetal Medicine and Surgery Service, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milan, Italy
Nicola Persico
Giuliana and Bernardo Caprotti Chair of Pediatrics, Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
Giovanni Montini
AuthorsValentina CaponeNicola PersicoGiovanni MontiniCorresponding authorCorrespondence to Valentina Capone.
Ethics declarations Competing interestsThe authors declare no competing interests.
About this articleCite this articleCapone, V., Persico, N. & Montini, G. Reply to ‘Management of very young fetuses with LUTO’. Nat Rev Urol (2022). https://doi.org/10.1038/s41585-022-00637-7
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