Risk Factors That Make Women More Susceptible to UTI
Table I outlines individual factors shown to increase the risk of getting a UTI.[6,7,8] In most women with repeated episodes of infection, multiple risk factors combine to cause the problem. Women with uncomplicated UTIs, by definition, do not have any urinary system abnormalities (ie, congenital malformation, urinary tract obstruction, or malfunction). However, women have a much shorter urethra than men, which allows bacteria to ascend more easily into the bladder. Many women begin to have cystitis after they become sexually active because intercourse increases the inoculation of bacteria into the bladder. In addition, delayed postcoital urination and the use of a diaphragm and a spermicide may further predispose sexually active women to recurrent infections. A history of recent UTI and/or persistent symptoms for at least 7 days may increase the risk of relapsing infection due to occult kidney infection, particularly for women of lower socioeconomic status.[9] Although there are several hypotheses for why a subgroup of women may be predisposed to frequent UTI relapses, a subclinical or "silent" pyelonephritis provides one explanation. Localization studies that have utilized such methods as the bladder washout test, selective ureteral catheterization, or antibody-coated bacteria tests have demonstrated that between 10%-35% of women with acute uncomplicated cystitis symptoms have a clinically unrecognized infection of the kidney.[10,11,12]
Some women with repeated Escherichia coli infections may also be genetically predisposed to this problem. A detailed family history may suggest a strong familial association for frequent infections among 2 or more female family members. Recent studies have demonstrated that these women have an increased density of normal uroepithelial carbohydrate receptors to which certain types of E coli designated uropathogenic strains (ie, serotypes O2, O4, O8, O18ab, O75, and O150) adhere.[13,14,15] Uropathogenic E coli belong to several distinct bacterial clones[14] that exhibit well-described virulence factors (eg, increased adherence to vaginal and uroepithelial cells, increased quantities of K capsular antigen, and the ability to produce a hemolysin, Fig. 2).[15,16,17,18]
Figure 2. Uropathogenic E. coli strains exhibit well described virulence factors (eg, increased adherence to vaginal and uroepithelial cells via surface pili, increased quantities of K capsular antigen, and the ability to produce a hemolysin). Adapted from Salit IE: Pathogenesis of UTI. In Urinary Tract Infection (slides and lecture notes), Copyright (c) 1990, Irving E. Salit, MD.
A number of adhesins of uropathogenic E coli strains have been characterized and studied as to their role in the pathogenesis of UTIs.[5,6] Type 1, or common type fimbriae or pili, are produced by many Enterobacteriaceae (including E coli) and have been shown to bind to mannoside residues on vaginal epithelial and uroepithelial cells.[6,8,15,17] Since this binding can be competitively inhibited by a methyl mannoside, these naturally occurring carbohydrate receptors have been designated mannose sensitive (MS).
On the other hand, strains of E coli that cause kidney infections possess a different type of adhesin called a P pili of fimbriae on their outer surface, which allow these bacteria to adhere to another carbohydrate receptor--a-D-Gal-(1,4)-[[beta]]-D-Gal or globobiose--in the upper urinary tract of the host.[6,8,15,17,19] Since the binding of bacteria to these upper tract receptors is not inhibited by mannose, they were designated mannose resistant (MR). The genes in E coli that are involved in the synthesis and assembly of P pili have been designated pap (pyelonephritis associated pili).[6]
Genetic switching by phasic variation of the E coli bacterium, in order to display P pili on its outer surface versus a common type 1 pilus, allows these strains to ascend in the urinary tract and may also predispose patients to kidney infection. ABO blood group has been shown to influence the availability of uroepithelial receptors for attachment of uropathogenic E coli.[20,21] Studies have shown that uroepithelial cells from women who do not secrete blood group antigens (nonsecretors) have specific surface adhesions (ie, E coli binding glycolipids), whereas women who secrete blood group antigens do not have these adhesions. Nonsecretor women also were more likely to have recurrent UTIs due to E coli. Therefore, the density of mucosal surface receptors that are able to bind bacteria in the urinary tract may be higher in some women than in others who have fewer of these receptors, genetically predisposing a subgroup of women to more frequent or recurrent E coli UTIs. These women may also have an increased colonization of the vaginal epithelium with uropathogenic E coli due to an increased density of MS receptors, and this may act as a source for frequent reinfections.[8,15,17,19] Alternatively, having certain bladder-surface glycoproteins, called Lewis antigens, may be protective against UTIs in people who have these antigens by covering carbohydrate receptors to which bacteria can adhere.[6]
Medscape General Medicine. 1996;1(1) © 1996
Cite this: Can a Silent Kidney Infection or Genetic Predisposition Underlie Recurrent UTIs? - Medscape - Oct 07, 1996.
