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.

Keywords: Innate immunity; Kidney; Renal fibrosis; Sex differences; Urinary tract infection.

Fig. 1

Schematic representation of age-related incidence of UTI in males (blue) and females (red). In the first six months of life, boys suffer more UTIs than girls (see inset); this relationship has reversed by 12 months of age, after which females dominate UTI incidence over much of the lifespan. Incidence of UTI rises in postmenopausal women and also in older men, where it is related to prostatic enlargement and associated urodynamic abnormalities

Fig. 2

Photomicrograph exemplifying the severe pyelonephritis observed in C3H male mice, 14 days post inoculation of the bladder with UPEC. Findings include tubular necrosis, extensive inflammation, and micro- and gross abscess formation (hematoxylin and eosin staining; scale bar, 200 μm)