Current applications of in utero intervention for lower urinary tract obstruction

Smith‐Harrison, Luriel I.; Hougen, Helen Y.; Timberlake, Matthew D.; Corbett, Sean T.

doi:10.1016/j.jpurol.2015.07.012

Cited by 31 publications

(15 citation statements)

References 45 publications

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“…Despite the fact that valve ablation surgery can considerably improve voiding dysfunction in most PUV patients, the symptoms including enuresis, urinary frequency, and poor bladder emptying persisted in some patients and required further and often long-term treatment (19,43). Currently, anticholinergics, clean intermittent catheterization, intradetrusor Botulinum toxin injections, overnight drainage, ␣-adrenergic blockers, and, finally, bladder augmentation are the treatment modalities used to manage bladder dysfunction in PUV patients.…”

Section: Discussionmentioning

confidence: 99%

Preventative effects of a HIF inhibitor, 17-DMAG, on partial bladder outlet obstruction-induced bladder dysfunction

Iguchi

Dönmez

Malykhina

et al. 2017

American Journal of Physiology-Renal Physiology

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Posterior urethral valves are the most common cause of partial bladder outlet obstruction (PBOO) in the pediatric population. Pathological changes in the bladder developed during PBOO are responsible for long-lasting voiding dysfunction in this population despite early surgical interventions. Increasing evidence showed PBOO induces an upregulation of hypoxia-inducible factors (HIFs) and their transcriptional target genes, and they play a role in pathophysiological changes in the obstructed bladders. We hypothesized that blocking HIF pathways can prevent PBOO-induced bladder dysfunction. PBOO was surgically created by ligation of the bladder neck in male C57BL/6J mice for 2 wk. PBOO mice received intraperitoneal injection of either saline or 17-DMAG (alvespimycin, 3 mg/kg) every 48 h starting from postsurgery. Sham-operated animals received injection of saline on the same schedule as PBOO mice and served as controls. The bladders were harvested after 2 wk, and basal activity and evoked contractility of the detrusor smooth muscle (DSM) were evaluated in vitro. Bladder function was assessed in vivo by void spot assay and cystometry in conscious, unrestrained mice. Results indicated the 17-DMAG treatment preserved DSM contractility and partially prevented the development of detrusor over activity in obstructed bladders. In addition, PBOO caused a significant increase in the frequency of micturition, which was significantly reduced by 17-DMAG treatment. The 17-DMAG treatment improved urodynamic parameters, including increases in the bladder pressure at micturition and nonvoid contractions observed in PBOO mice. These results demonstrate that treatment with 17-DMAG, a HIF inhibitor, significantly alleviated PBOO-induced bladder pathology in vivo.

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Section: Discussionmentioning

confidence: 99%

Preventative effects of a HIF inhibitor, 17-DMAG, on partial bladder outlet obstruction-induced bladder dysfunction

Iguchi

Dönmez

Malykhina

et al. 2017

American Journal of Physiology-Renal Physiology

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“…Randomised controlled trials are underway to clarify the role of fetal cystoscopy and vesico‐amniotic shunting in fetal megacystis . Nevertheless, it is likely that the most significant single determinant of outcome is disease severity rather than the type or timing of fetal intervention…”

Section: Discussionmentioning

confidence: 99%

Fetal megacystis: Institutional experience and outcomes

Taghavi

Sharpe

Stringer

et al. 2017

Aust NZ J Obst Gynaeco

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“…The other remaining challenge is to investigate the best therapeutic modality after risk stratification. Previous studies have compared VAS versus no fetal therapy, or fetal cystoscopy versus no fetal intervention . The aims of the randomized‐controlled PLUTO trail were to determine the efficacy and safety of VAS in lower urinary tract obstruction.…”

Section: Discussionmentioning

confidence: 99%

Prediction model of postnatal renal function in fetuses with lower urinary tract obstruction (LUTO)—Development and internal validation

et al. 2019

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Objective To develop a prediction model of postnatal renal function in fetuses with lower urinary tract obstruction (LUTO) based on fetal ultrasound parameters and amniotic fluid volume. Methods Retrospective nationwide cohort study of fetuses with postnatally confirmed LUTO and known eGFR. Fetuses treated with fetal interventions such as vesico‐amniotic shunting or cystoscopy were excluded. Logistic regression analysis was used to identify prognostic ultrasound variables with respect to renal outcome following multiple imputation of missing data. On the basis of these fetal renal parameters and amniotic fluid volume, a model was developed to predict postnatal renal function in fetuses with LUTO. The main study outcome was an eGFR less than 60 mL/min * 1.73 m2 based on the creatinine nadir during the first year following diagnosis. Model performance was evaluated by receiver operator characteristic (ROC) curve analysis, calibration plots, and bootstrapping. Results Hundred one fetuses with a confirmed diagnosis of LUTO were included, eGFR less than 60 was observed in 40 (39.6%) of them. Variables predicting an eGFR less than 60 mL/min * 1.73m2 included the following sonographic parameters: hyperechogenicity of the renal cortex and abnormal amniotic fluid volume. The model showed fair discrimination, with an area under the ROC curve of 0.70 (95% confidence interval, 0.59‐0.81, 0.66 after bootstrapping) and was overall well‐calibrated. Conclusion This study shows that a prediction model incorporating ultrasound parameters such as cortical appearance and abnormal amniotic fluid volume can fairly discriminate an eGFR above or below 60 mL/min * 1.73m2. This clinical information can be used in identifying fetuses eligible for prenatal interventions and improve counseling of parents.

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Current applications of in utero intervention for lower urinary tract obstruction

Cited by 31 publications

References 45 publications

Preventative effects of a HIF inhibitor, 17-DMAG, on partial bladder outlet obstruction-induced bladder dysfunction

Preventative effects of a HIF inhibitor, 17-DMAG, on partial bladder outlet obstruction-induced bladder dysfunction

Fetal megacystis: Institutional experience and outcomes

Prediction model of postnatal renal function in fetuses with lower urinary tract obstruction (LUTO)—Development and internal validation

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