Recurrent Urinary Tract Infection Incidence Rates Decrease in Women With Cystitis Cystica After Treatment With d-Mannose: A Cohort Study

Abstract

Objectives: D-Mannose is a promising nonantibiotic prophylaxis for recurrent urinary tract infection (rUTI). Recurrent UTI is common in postmenopausal women and may be especially prevalent in those with cystitis cystica (CC) lesions found on cystoscopy. Our objectives were to determine whether CC lesions are associated with a higher UTI incidence rate and whether D-mannose reduces this rate in women with CC.Methods: This is a retrospective cohort study of patients with rUTI who underwent cystoscopy at our institution (from which CC status was identified) and who were treated with D-mannose as a single agent for UTI prophylaxis. Participants were required to have at least 1 year of follow-up for UTIs both before and after D-mannose initiation to allow for a pre-post comparison.Results: Twenty-seven patients were included in the analysis (13 with CC, 14 without CC). Most patients (88.9%) were postmenopausal. Patients with CC had a higher UTI incidence rate than patients without CC (4.69 vs 2.93 UTIs/year before starting D-mannose prophylaxis, P = 0.021). After initiating D-mannose prophylaxis, the UTI incidence rate decreased significantly in patients with CC (rate decrease = 2.23 UTIs/year, P = 0.0028). This decrease was similar in magnitude to that observed in patients without CC (rate decrease = 1.64 UTIs/year, P = 0.0007; P interaction = 0.58).Conclusions: Patients with rUTI with CC had more frequent UTI episodes than patients without CC. Patients in both groups had fewer UTI episodes after beginning D-mannose prophylaxis. These findings add to the body of literature supporting D-mannose for the prevention of rUTI in women, including those with CC.

D-mannose ameliorates age-associated cellular senescence in the bladder urothelium and NLRP3/Gasdermin/IL-1β -driven pyroptotic epithelial cell shedding

“…In line with this, mannose has been reported to protect against intestinal barrier dysfunction in a (young) mouse model of colitis (Dong et al, 2022). Moreover, we have recently reported that D-mannose prophylaxis led to a significant decrease in UTI incidence rate in patients with bTLT (Chiu et al, 2022).…”

“…Several clinical investigations have described the benefits of D-mannose in patients suffering from rUTI (Chiu et al, 2022; Kranjčec et al, 2014; Parazzini et al, 2022). D-mannose is known to bind to UPEC adhesin protein FimH and thus prevent them from adhering to bladder epithelial cells (reviewed in Lupo et al, 2021).…”

“…In line with this, mannose has been reported to protect against intestinal barrier dysfunction in a (young) mouse model of colitis (Dong et al, 2022). Moreover, we have recently reported that D-mannose prophylaxis led to a significant decrease in UTI incidence rate in patients with bTLT (Chiu et al, 2022). Thus, D-mannose treatment might produce far-reaching urothelial cell intrinsic and extrinsic reversal of age-associated changes in addition to limiting rUTI frequency.…”

“…Finally, we report on the utility of a simple sugar monosaccharide, D-mannose, as a surprisingly effective senotherapeutic in limiting pyroptotic epithelial cell death, reversing cell cycle arrest, limiting SASP, and restoring autophagic flux that is otherwise notably increased in non-treated aged mice. D-Mannose is a sugar that is considered as an alternative treatment to UTIs (Chiu et al, 2022; Lenger et al, 2020) as it binds to the adhesion protein FimH on uropathogens and prevents their adherence to bladder epithelial cells (Scribano et al, 2020) and has been known to decrease secretion of inflammatory cytokines (Ala-Jaakkola et al, 2022). Our results show that D-mannose has a cell intrinsic impact in addition to the known extrinsic roles, as treatment reduces accumulation of SA-β-galactosidase and activates autophagic flux.…”

Bladder Mucosal Cystitis Cystica Lesions Are Tertiary Lymphoid Tissues That Correlate With Recurrent Urinary Tract Infection Frequency in Postmenopausal Women

“…Initiation of D-mannose prophylaxis led to a significant decrease in UTI incidence rate in patients with CC. 18 Thus, the use of cystoscopy to assess for CC and developing therapies targeted at reducing the formation or maturation of CC lesions may be beneficial for improving women's lower urinary tract health.…”