02888nas a2200481 4500008004100000022001400041245008700055210006900142260001300211300001200224490000700236520154100243653000901784653002201793653001601815653001501831653002801846653002501874653001501899653002401914653001101938653003101949653001801980653001101998653001402009653002802023653000902051653003202060653001502092100002502107700001902132700001602151700001902167700002402186700002202210700002502232700002402257700002202281700002402303700002302327700002002350856003602370 2015 eng d a1523-175500aUrinary uromodulin, kidney function, and cardiovascular disease in elderly adults.0 aUrinary uromodulin kidney function and cardiovascular disease in c2015 Nov a1126-340 v883 a

Urinary uromodulin (uUMOD) is the most common secreted tubular protein in healthy adults. However, the relationship between uUMOD and clinical outcomes is still unclear. Here we measured uUMOD in 192 participants of the Cardiovascular Health Study with over a 30% decline in estimated glomerular filtration rate (eGFR) over 9 years, 54 with incident end-stage renal disease (ESRD), and in a random subcohort of 958 participants. The association of uUMOD with eGFR decline was evaluated using logistic regression and with incident ESRD, cardiovascular disease, heart failure, and mortality using Cox proportional regression. Mean age was 78 years and median uUMOD was 25.8 μg/ml. In a case-control study evaluating eGFR decline (192 cases and 231 controls), each 1-s.d. higher uUMOD was associated with a 23% lower odds of eGFR decline (odds ratio 0.77 (95% CI 0.62-0.96)) and a 10% lower risk of mortality (hazard ratio 0.90 (95% CI 0.83-0.98)) after adjusting for demographics, eGFR, albumin/creatinine ratio, and other risk factors. There was no risk association of uUMOD with ESRD, cardiovascular disease, or heart failure after multivariable adjustment. Thus, low uUMOD levels may identify persons at risk of progressive kidney disease and mortality above and beyond established markers of kidney disease, namely eGFR and the albumin/creatinine ratio. Future studies need to confirm these results and evaluate whether uUMOD is a marker of tubular health and/or whether it plays a causal role in preserving kidney function.

10aAged10aAged, 80 and over10aAlbuminuria10aBiomarkers10aCardiovascular Diseases10aCase-Control Studies10aCreatinine10aDisease Progression10aFemale10aGlomerular Filtration Rate10aHeart Failure10aHumans10aIncidence10aKidney Failure, Chronic10aMale10aProportional Hazards Models10aUromodulin1 aGarimella, Pranav, S1 aBiggs, Mary, L1 aKatz, Ronit1 aIx, Joachim, H1 aBennett, Michael, R1 aDevarajan, Prasad1 aKestenbaum, Bryan, R1 aSiscovick, David, S1 aJensen, Majken, K1 aShlipak, Michael, G1 aChaves, Paulo, H M1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/677002938nas a2200205 4500008004100000022001400041245009500055210006900150260001600219520228600235100002502521700002002546700001902566700002102585700002402606700002202630700002402652700002002676856003602696 2016 eng d a1523-683800aUrinary Uromodulin and Risk of Urinary Tract Infections: The Cardiovascular Health Study.0 aUrinary Uromodulin and Risk of Urinary Tract Infections The Card c2016 Oct 283 a

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) μg/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 (>38.93μg/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 (≤17.26μg/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.

1 aGarimella, Pranav, S1 aBartz, Traci, M1 aIx, Joachim, H1 aChonchol, Michel1 aShlipak, Michael, G1 aDevarajan, Prasad1 aBennett, Michael, R1 aSarnak, Mark, J uhttps://chs-nhlbi.org/node/7369