Antenatal biological models in the characterization and research of congenital lower urinary tract disorders.

Congenital lower urinary tract disorders are a family of diseases affecting both urinary storage and voiding as well as upstream kidney function. Current treatments include surgical reconstruction but many children still fail to achieve urethral continence or progress to chronic kidney disease. New therapies can only be achieved through undertaking research studies to enhance our understanding of congenital lower urinary tract disorders. Animal models form a critical component of this research, a corner of the triangle composed of human in-vitro studies and clinical research. We describe the current animal models for two rare congenital bladder disorders, posterior urethral valves (PUV) and bladder exstrophy (BE). We highlight important areas for researchers to consider when deciding which animal model to use to address particular research questions and outline the strengths and weaknesses of current models available for PUV and BE. Finally, we present ideas for refining animal models for PUV and BE in the future to stimulate future researchers and help them formulate their thinking when working in this field.

Antenatal urodynamic studies in the fetal lamb: experimental protocol and preliminary results.

OBJECTIVES: To set up a fetal lamb model for intrauterine fetal urodynamic studies. METHODS: Fourteen fetal lambs underwent placement of a bladder catheter at a mean gestational age of 87 days. Three fetuses also had a partial urethral obstruction by the simultaneous placement of a peri-urethral constricting ring. Urodynamic and ultrasound studies were performed weekly by the filling cystometry method. RESULTS: Hundred and six voiding cycles were recorded during 25 urodynamic studies between 84- and 133-days gestation. All voiding profiles were biphasic with a mean duration of 4.2 min (range 1-10), a mean voiding pressure of 23 cm of water (range 7-33) and a mean periodicity of 19.2 min (range 11-50). The obstructed animals had bladder overactivity. This correlated with ultrasound and post-mortem findings of megacystis and bilateral hydroureteronephrosis. The fetal mortality rate was 85.7% and the mean duration of survival post surgery was 45 +/- 5.7 days. CONCLUSION: Serial urodynamic studies could be performed in a fetal lamb model. Following partial urethral obstruction, bladder overactivity was observed.