Dataset Information

Urinary Uromodulin and Risk of Urinary Tract Infections: The Cardiovascular Health Study.

ABSTRACT: 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.Prospective longitudinal cohort study.953 participants enrolled in the Cardiovascular Health Study.Uromodulin assayed using enzyme-linked immunosorbent assay in spot urine samples.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.Median uromodulin level was 25.9 (IQR, 17.3-38.9) ?g/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 (>38.93?g/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 (?17.26?g/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).Use of ICD-9 codes to identify outcomes and lack of generalizability to younger populations.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.

SUBMITTER: Garimella PS

PROVIDER: S-EPMC5409878 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Urinary Uromodulin and Risk of Urinary Tract Infections: The Cardiovascular Health Study.

Garimella Pranav S PS Bartz Traci M TM Ix Joachim H JH Chonchol Michel M Shlipak Michael G MG Devarajan Prasad P Bennett Michael R MR Sarnak Mark J MJ

American journal of kidney diseases : the official journal of the National Kidney Foundation 20161028 6

<h4>Background</h4>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.<h4>Study design</h4>Prospective longitudinal cohort study.<h4>Setting & participants</h4>953 participants enrolled in the Cardiovascular Health Study.<h4>Predictor</h4>Uromodulin assayed using enzyme-linked immunosorbent assay in spot urine samples ...[more]

PMID: 28029393

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Project description:BACKGROUND:Cranberries (particularly in the form of cranberry juice) have been used widely for several decades for the prevention and treatment of urinary tract infections. The aim of this review is to assess the effectiveness of cranberries in treating such infections. OBJECTIVES:To assess the effectiveness of cranberries for the treatment of urinary tract infections. SEARCH STRATEGY:The search strategy developed by the Cochrane Renal Group was used. Also, companies involved with the promotion and distribution of cranberry preparations were contacted; electronic databases and the Internet were searched using English and non English language terms; reference lists of review articles and relevant trials were also searched. SELECTION CRITERIA:All randomised or quasi randomised controlled trials of cranberry juice or cranberry products for the treatment of urinary tract infections. Trials of men, women or children were included. DATA COLLECTION AND ANALYSIS:Titles and abstracts of studies that were potentially relevant to the review were screened by one reviewer, RJ, who discarded studies that were clearly ineligible but aimed to be overly inclusive rather than risk losing relevant studies. Reviewers RJ and LM independently assessed whether the studies met the inclusion criteria. Further information was sought from the authors where papers contained insufficient information to make a decision about eligibility. MAIN RESULTS:No trials were found which fulfilled all of the inclusion criteria. Two trials were excluded because they did not have any relevant outcomes. REVIEWER'S CONCLUSIONS:After a thorough search, no randomised trials which assessed the effectiveness of cranberry juice for the treatment of urinary tract infections were found. Therefore, at the present time, there is no good quality evidence to suggest that it is effective for the treatment of urinary tract infections. Well-designed parallel group, double blind trials comparing cranberry juice and other cranberry products versus placebo to assess the effectiveness of cranberry juice in treating urinary tract infections are needed. Outcomes should include reduction in symptoms, sterilisation of the urine, side effects and adherence to therapy. Dosage (amount and concentration) and duration of therapy should also be assessed. Consumers and clinicians will welcome the evidence from these trials.

Project description:BackgroundUromodulin (UMOD) is released by renal tubular cells into the serum (sUMOD) and urine. Lower urine UMOD has been linked to mortality and cardiovascular disease but much less is known about sUMOD. We evaluated the association of sUMOD with these outcomes in community-dwelling older adults.MethodsWe measured sUMOD in a random subcohort of 933 participants enrolled in the Cardiovascular Health Study. The associations of sUMOD with all-cause mortality, incident heart failure (HF) and incident cardiovascular disease (CVD; myocardial infarction, stroke and mortality due to coronary disease or stroke) were evaluated using multivariable Cox regression, adjusting for study participants' demographics, estimated glomerular filtration rate (eGFR), albuminuria and CVD risk factors. Generalized additive models with splines were used to address the functional form of sUMOD with outcomes. Due to nonlinear associations of sUMOD with all outcomes, 2.5% of the values on either end of the sUMOD distribution were excluded from the analyses, limiting the range of sUMOD to 34.3-267.1 ng/mL.ResultsThe mean age was 78 ± 5 years, 40% were male, sUMOD level was 127 ± 64 ng/mL, eGFR was 63 mL/min/1.73 m2 and 42% had CKD defined as eGFR <60 mL/min/1.73 m2. Patients in the lower sUMOD quartiles had lower eGFR and higher albuminuria (P < 0.01, respectively). During a median follow-up of 9.9 years, 805 patients died, 283 developed HF and 274 developed CVD. In multivariable analysis, higher sUMOD was significantly associated with a lower hazard for mortality {hazard ratio [HR] 0.89 [95% confidence interval (CI) 0.80-0.99] per 1 standard deviation (SD) higher sUMOD}, CVD [HR 0.80 (95% CI 0.67-0.96)] and the composite endpoint [HR 0.88 (95% CI 0.78-0.99)]; the association with HF was not statistically significant [HR 0.84 (95% CI 0.70-1.01)].ConclusionHigher sUMOD is independently associated with a lower risk for mortality and CVD in older adults.

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Urinary Uromodulin and Risk of Urinary Tract Infections: The Cardiovascular Health Study.

Publications

Urinary Uromodulin and Risk of Urinary Tract Infections: The Cardiovascular Health Study.

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