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Sex effects in pyelonephritis

Abstract

Urinary tract infections (UTIs) are generally considered a disease of women. However, UTIs affect females throughout the lifespan, and certain male populations (including infants and elderly men) are also susceptible. Epidemiologically, pyelonephritis is more common in women but carries increased morbidity when it does occur in men. Among children, high-grade vesicoureteral reflux is a primary risk factor for upper-tract UTI in both sexes. However, among young infants with UTI, girls are outnumbered by boys; risk factors include posterior urethral valves and lack of circumcision. Recent advances in mouse models of UTI reveal sex differences in innate responses to UTI, which vary somewhat depending on the system used. Moreover, male mice and androgenized female mice suffer worse outcomes in experimental pyelonephritis; evidence suggests that androgen exposure may suppress innate control of infection in the urinary tract, but additional androgen effects, as well as non-hormonal sex effects, may yet be specified. Among other intriguing directions, recent experiments raise the hypothesis that the postnatal testosterone surge that occurs in male infants may represent an additional factor driving the higher incidence of UTI in males under 6 months of age. Ongoing work in contemporary models will further illuminate sex- and sex-hormone-specific effects on UTI pathogenesis and immune responses.

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Funding

This work was supported by National Institutes of Health (NIH) grants R01-DK111541 and R01-DK108840; T.N.H. was supported by NIH grant T32-DK007126.

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Correspondence to David A. Hunstad.

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D.A.H. serves on the Board of Directors of BioVersys AG, Basel, Switzerland. The other authors have no potential conflicts to disclose.

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Albracht, C.D., Hreha, T.N. & Hunstad, D.A. Sex effects in pyelonephritis. Pediatr Nephrol (2020). https://doi.org/10.1007/s00467-020-04492-9

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Keywords

  • Sex differences
  • Urinary tract infection
  • Innate immunity
  • Kidney
  • Renal fibrosis