Serum uromodulin and decline of kidney function in older participants of the population-based KORA F4/FF4 study.

BACKGROUND: Uromodulin, a tissue-specific tubular glycoprotein, has recently emerged as a promising biomarker for kidney function and tubular integrity. However, the association of serum uromodulin (sUmod) with renal function decline is still unknown in an older general population. METHODS: We analysed the association of sUmod with the estimated glomerular filtration rate (eGFR) and albuminuria in 1075 participants of the population-based Cooperative Health Research in the Region of Augsburg (KORA) F4 study, ages 62-81 years, at baseline and prospectively after a mean follow-up time of 6.5 years (n = 605) using logistic and linear regression models as well as receiver operating characteristics (ROC) analyses. RESULTS: Cross-sectionally, sUmod was positively associated with eGFR (ß = 0.31 ± 0.02 per higher standard deviation sUmod; P < 0.001) and inversely associated with the urinary albumin:creatinine ratio (ß = -0.19 ± 0.04; P < 0.001) after adjustment for sex, age, body mass index, arterial hypertension, prediabetes and diabetes. After multivariable adjustment including baseline eGFR, sUmod was not associated with incident chronic kidney disease (CKD), defined as a decrease in eGFR <60 mL/min/1.73 m2 after 6.5 years of follow-up {odds ratio [OR] 1.02 [95% confidence interval (CI) 0.77-1.36] per higher SD sUmod} but was inversely associated with advanced CKD, defined as incident eGFR <45 mL/min/1.73 m2 [OR 0.64 (95% CI 0.42-0.98)]. The ROC showed no added predictive value of sUmod for kidney function decline in the fully adjusted model. CONCLUSIONS: Higher sUmod was inversely associated with progression to advanced kidney disease but does not provide additional predictive value for the development of CKD in elderly participants of the population-based KORA study.

Serum uromodulin and risk for cardiovascular morbidity and mortality in the community-based KORA F4 study.

BACKGROUND AND AIMS: Serum uromodulin, a novel biomarker of kidney function and tubular integrity, has been linked to cardiovascular events and total mortality in patients at high cardiovascular risk. Here, we analyze the association of serum uromodulin with cardiovascular morbidity and cardiovascular as well as total mortality in the population-based KORA F4 study stratified by sex. METHODS: Baseline serum uromodulin was measured in 1079 participants of the KORA F4 study (age 62-81 years). Using multivariable adjusted Cox proportional hazards models, the associations of serum uromodulin with total mortality and cardiovascular mortality were analyzed after a median follow-up period of 8.6 years, and with non-fatal and fatal stroke and myocardial infarction/coronary death after a median follow-up time of 8.4 years. RESULTS: Serum uromodulin was significantly inversely associated with total mortality (HR 0.65; 95% CI 0.53-0.79 per standard deviation of logarithmized serum uromodulin; p < 0.001) and cardiovascular mortality (HR 0.70; 95% CI 0.52-0.93) in men, but not in women (HR for all-cause mortality in women 0.98; 95% CI 0.77-1.25, HR for cardiovascular mortality 0.78; 95% CI 0.56-1.11) after adjustment for age, BMI, diabetes and eGFR. In addition, serum uromodulin was significantly inversely associated with incident stroke in men (HR 0.68; 95% CI 0.50-0.92), but not in women (HR 0.96; 95% CI 0.68-1.38) after multivariable adjustment. The association of serum uromodulin with incident myocardial infarction was attenuated and lost significance after multivariable adjustment in both sexes. CONCLUSIONS: Serum uromodulin is an independent biomarker for total and cardiovascular mortality in men from the general community aged 62 years or older.

Serum uromodulin is inversely associated with arterial hypertension and the vasoconstrictive prohormone CT-proET-1 in the population-based KORA F4 study.

OBJECTIVES: Uromodulin has been associated with arterial hypertension in genome-wide association studies, but data from clinical and preclinical studies are inconsistent. We here analyzed the association of serum uromodulin (sUmod) with arterial hypertension and vasoactive hormones in a population-based study. METHODS: In 1108 participants of the KORA F4 study aged 62-81 years, sUmod was measured and the association of sUmod with arterial hypertension was assessed using logistic regression models. The associations of sUmod with renin and aldosterone and with the vasoconstrictive prohormone C-terminal pro-endothelin-1 (CT-proET-1) were analyzed in 1079 participants and in 618 participants, respectively, using linear regression models. RESULTS: After multivariable adjustment including sex, age, eGFR, BMI, fasting glucose, current smoking, previous stroke and myocardial infarction, sUmod was inversely associated with arterial hypertension (OR 0.78; 95% CI 0.68-0.91; p = 0.001). SUmod was not significantly associated with renin and aldosterone after adjustment for sex, age and eGFR. However, sUmod was inversely associated with CT-proET-1 (ß -0.19 ± 0.04; p < 0.001) after adjustment for sex, age, eGFR, BMI, arterial hypertension, fasting glucose, current smoking, previous stroke and myocardial infarction. The association with CT-proET-1 was stronger in participants with hypertension (ß -0.22 ± 0.04) than in normotensive participants (ß -0.13 ± 0.06; p for interaction hypertension = 0.003 in the model adjusted for hypertension). CONCLUSIONS: SUmod was inversely associated with arterial hypertension and the vasoconstrictive prohormone CT-proET-1, suggesting direct or indirect effects of sUmod on blood pressure regulation.