Back to 2014 Fall Congress Meeting Abstracts

BACKGROUND:
Obstructive nephropathy and bladder dysfunction are among the most common causes of ESRD in children. We study a unique mouse model, the megabladder (mgb) mouse, that in the homozygous (mgb-/-) state has a non-functional overdistended bladder at birth, with progressive hydronephrosis. This model mimics features of non-neurogenic neurogenic bladder, prune-belly syndrome or PUV. We previously reported that vesicostomy could be life saving to these mice. However, up to 35% of them developed urinary stones and the intravesical suture was identified as the nidus. In this work we report and investigate the incidence of spontaneous infection and stone formation in mgb-/- mice that have not undergone surgical intervention.
METHODS:
We identified 10 mgb-/- mice in our colony (8 females and two males) that had spontaneous bladder stones; two of them had also kidney stones. None had undergone any surgical intervention. Mean age at stone diagnosis was 42.2 days. We also identified spontaneous UTI without stones in 6 other mgb-/- mice. To study the incidence of spontaneous uronephrolithiasis and UTI we determined that a cohort of 17 animals would provide >80% power to detect the outcome at a frequency of 5% and 90% power to detect a frequency of 10%. We therefore examined a cohort of 19 consecutive mgb-/- female mice by ultrasonography at 4 weeks of age. A concurrent urine sample was obtained by percutaneous bladder tapping and tested for pH and culture. If no stones were present we repeated the ultrasound and urine tests at 6 and 8 weeks of age. At the termination of the 8-week period, or if a stone was discovered at any point, mice were euthanized and tissues collected for culture and histopathology. Stones were sent for chemical analysis.
RESULTS:
In the general mgb colony, we identified a total of 16 mice with spontaneous stones over a 6 months period. All were mgb-/- genotype. We performed urine, stone and tissue cultures on 12 of them, and the results were positive in 11 (91.7%). In the same time period we also identified 11 mgb-/- mice with urinary infection and no stones. Recovered organisms included Coagulase negative Staphylococcus, Bacillus non anthracis, and Escherichia coli. Urine pH was consistently alkaline (7.5-8) in affected mice, as opposed to mice with no infection or stones (pH 5.5-6). When looking at the designated cohort of 19 consecutive Mgb-/- females, we identified bladder stones in 6 mice (cumulative incidence 31.6%), and urinary infection was diagnosed in 8 (cumulative incidence 42.1%) including the 6 mice with stones. The predominant stone composition was struvite, with up to 10% apatite. The average stone weight was 0.118g. Histopathology showed bladder and kidney inflammatory changes and scarring in some of the infected kidneys.
CONCLUSIONS:
In contrast to our previous assumption that a stone would only develop in the megabladder mouse in the presence of a specific nidus, we are now finding spontaneous stones and infection in mgb-/- mice. We propose this as a novel animal model of UTI and uronephrolithiasis in bladder dysfunction and urinary stasis.