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Urinary Uromodulin and Risk of Urinary Tract Infections: The Cardiovascular Health Study
Pranav S Garimella1, Traci M Bartz2, Joachim H Ix3
1Tufts Medical Center, Boston, MA.
Insights
Higher urinary uromodulin levels significantly reduce the risk of urinary tract infections (UTI) in older adults. This finding supports uromodulin
Area of Science:
- Urology
- Nephrology
- Epidemiology
Background:
- Laboratory studies suggest urinary uromodulin may protect against urinary tract infections (UTI).
- Epidemiologic studies evaluating this relationship in humans are lacking.
Purpose of the Study:
- To investigate the association between urinary uromodulin levels and the risk of UTI in humans.
- To determine if urinary uromodulin has a protective effect against UTI in a human cohort.
Main Methods:
- Prospective longitudinal cohort study of 953 participants in the Cardiovascular Health Study.
- Urinary uromodulin levels were measured using enzyme-linked immunosorbent assay.
- UTI events were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes.
Main Results:
- Participants in the highest quartile of uromodulin concentration had a significantly lower risk for composite UTI outcomes (IRR, 0.47).
- This association remained significant for outpatient UTI events, even after excluding participants with prior UTI (IRR, 0.42).
- High urinary uromodulin levels were associated with a lower risk for UTI, independent of traditional risk factors.
Conclusions:
- High urinary uromodulin levels are associated with a reduced risk of UTI in older community-dwelling adults.
- Findings support laboratory data suggesting a protective role for uromodulin against UTI.
- Further research is warranted to explore uromodulin-based UTI prevention or treatment strategies.
Background:
Laboratory studies suggest that urinary uromodulin, the most common protein in the urine of healthy adults, may protect against urinary tract infection (UTI). Epidemiologic studies evaluating this relationship in humans are lacking.
Study Design:
Prospective longitudinal cohort study.
Setting & Participants:
953 participants enrolled in the Cardiovascular Health Study.
Predictor:
Uromodulin assayed using enzyme-linked immunosorbent assay in spot urine samples.
Outcomes:
Composite of outpatient UTI events or UTI-related hospitalizations and each of them individually identified using International Classification of Diseases, Ninth Revision (ICD-9) codes using negative binomial regression with robust standard errors adjusted for age, race, sex, body mass index, diabetes, estimated glomerular filtration rate, and urinary albumin and urinary creatinine excretion.
Results:
Median uromodulin level was 25.9 (IQR, 17.3-38.9) microg/mL, mean age of participants was 78 years, 61% were women, and 15% were black. There were 331 outpatient UTI events and 87 UTI-related hospitalizations among 186 participants during a median 9.9 years of follow-up. Persons in the highest quartile (>38.93microg/mL) of uromodulin concentration had a significantly lower risk for the composite outcome (incidence rate ratio [IRR], 0.47; 95% CI, 0.29-0.79) compared with those in the lowest quartile (≤17.26microg/mL). This association remained significant for outpatient UTI events (highest vs lowest quartile even after excluding those with prior UTI: IRR, 0.42; 95% CI, 0.23-0.77). The direction of association with UTI hospitalization was similar, but not statistically significant (IRR, 0.78; 95% CI, 0.39-1.58).
Limitations:
Use of ICD-9 codes to identify outcomes and lack of generalizability to younger populations.
Conclusions:
High urinary uromodulin levels are associated with lower risk for UTI in older community-dwelling adults independent of traditional UTI risk factors. This finding supports prior laboratory data indicating a protective role of uromodulin against UTI. Further research is needed to understand if this may lead to new treatments to prevent or treat UTI.
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