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Vesicoureteral reflux induces renal trauma in a mouse model of ascending, unobstructed pyelonephritis
1Department of Medicine, University of Minnesota Medical School, Minneapolis.
Abstract:
To determine whether in a mouse model of ascending, unobstructed urinary tract infection an inoculum volume could be found that induces vesicoureteral reflux without causing renal injury, the occurrence of vesicoureteral reflux (identified by inspection, kidney culture, and histopathologic examination) was compared with the occurrence of renal trauma (identified by histopathologic examination and cultures of blood and spleen) in female Swiss Webster mice after transurethral inoculation with 50, 75, 100 or 150 microliters of a bacterial suspension containing India ink. Vesicoureteral reflux (which was more common the greater the inoculum volume) induced renal trauma even with small (50 microliters) inoculum volumes, accounting for the observed association of inoculum volume and renal injury. No single parameter of vesicoureteral reflux identified all refluxed or traumatized kidneys. Thus, careful attention to the avoidance of vesicoureteral reflux following inoculation, using multiple indicators of reflux, is needed if this model is to faithfully reproduce infections occurring in the nontraumatized human urinary tract.
Insights
Researchers investigated inoculum volumes in a mouse model for urinary tract infections. They found that even small volumes inducing vesicoureteral reflux also caused kidney injury, complicating infection modeling.
Area of Science:
- Urology
- Microbiology
- Pathology
Background:
- Ascending urinary tract infections (UTIs) are common.
- Mouse models are crucial for studying UTI pathogenesis.
- Vesicoureteral reflux (VUR) can lead to kidney damage.
Purpose of the Study:
- To identify an inoculum volume that causes VUR without renal injury in a mouse model.
- To understand the relationship between inoculum volume, VUR, and renal trauma.
Main Methods:
- Female Swiss Webster mice were transurethrally inoculated with varying volumes (50-150 µL) of bacterial suspension with India ink.
- VUR was assessed via inspection, kidney culture, and histopathology.
- Renal trauma was evaluated by histopathology and blood/spleen cultures.
Main Results:
- Increased inoculum volume correlated with a higher incidence of VUR.
- Even small inoculum volumes (50 µL) causing VUR also induced renal trauma.
- No single method reliably identified all kidneys with VUR or trauma.
Conclusions:
- Establishing a mouse model of ascending UTIs that avoids renal injury while inducing VUR is challenging.
- Multiple indicators are necessary to accurately detect VUR and renal trauma in this model.
- Careful control of inoculation parameters is essential for accurate UTI modeling.