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Interplay between vesicoureteric reflux and kidney infection in the development of reflux nephropathy in mice

Samantha E Bowen1, Christine L Watt, Inga J Murawski

  • 1Department of Molecular Genetics and Microbiology, Duke University, Duke University Medical Center, Durham, NC, USA.

Disease Models & Mechanisms
|March 23, 2013
PubMed

Insights

Vesicoureteric reflux (VUR) combined with sustained kidney infection is essential for developing reflux nephropathy. Sterile reflux or a single infection alone does not cause this condition in mice.

Area of Science:

  • Nephrology
  • Urology
  • Immunology
  • Pediatric Medicine

Background:

  • Vesicoureteric reflux (VUR) is a congenital urinary tract defect often diagnosed after urinary tract infections (UTIs).
  • VUR is linked to reflux nephropathy, characterized by chronic kidney inflammation and fibrosis, frequently following febrile UTIs.

Purpose of the Study:

  • To investigate the roles of VUR and Escherichia coli infection in reflux nephropathy development.
  • To analyze the impact of host immune response on reflux nephropathy in a C3H mouse model.

Main Methods:

  • Utilized C3H mice, which exhibit a 100% incidence of VUR.
  • Evaluated the effects of VUR alone, VUR with sustained E. coli kidney infection, and infection without reflux.
  • Compared renal inflammation and nephropathy in two refluxing C3H substrains (HeN and HeJ) with differing innate immunity.

Main Results:

  • Reflux nephropathy developed only when VUR was combined with sustained kidney infection; sterile reflux or single infections were insufficient.
  • HeJ mice, with impaired innate immunity and bacterial clearance, showed more severe renal inflammation and reflux nephropathy than HeN mice.
  • These findings highlight the critical interplay between VUR, persistent infection, and host immunity.

Conclusions:

  • Sustained kidney infection in the presence of VUR is crucial for developing reflux nephropathy.
  • Host immune response significantly influences the severity of renal damage in this VUR mouse model.
  • The study elucidates the synergistic factors contributing to reflux nephropathy pathogenesis.

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