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Updated: Jan 1, 2026
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Association of serum and urinary uromodulin and their correlates in older adults-The Cardiovascular Health Study
Dominik Steubl1,2, Petra Buzkova3, Joachim H Ix4
1Division of Nephrology, Department of Medicine, Tufts Medical Center, Boston, Massachusetts.
Insights
Serum uromodulin (sUMOD) correlates more strongly with estimated glomerular filtration rate (eGFR) than urine uromodulin (uUMOD). Their distinct associations with demographic and laboratory factors suggest differential regulation of renal tubular cell secretion.
Area of Science:
- Nephrology
- Biochemistry
- Cardiovascular Medicine
Background:
- Uromodulin (UMOD) is exclusively secreted by renal tubular cells into both serum (sUMOD) and urine (uUMOD).
- Both sUMOD and uUMOD correlate with estimated glomerular filtration rate (eGFR) and are linked to mortality and cardiovascular disease (CVD).
- Previous studies have not simultaneously measured sUMOD and uUMOD, limiting understanding of their relationship and independent correlates.
Purpose of the Study:
- To evaluate the simultaneous correlations of sUMOD and uUMOD with eGFR in a human cohort.
- To assess the associations of sUMOD and uUMOD with demographic, laboratory parameters, and CVD risk factors.
- To determine if sUMOD and uUMOD are independently associated with eGFR and other clinical factors.
Main Methods:
- Cross-sectional analysis of a random sub-cohort (n = 933) from the Cardiovascular Health Study.
- Measurement of serum and urine uromodulin (sUMOD, uUMOD) and estimated glomerular filtration rate (eGFR).
- Multivariable linear regression analysis to assess correlations and independent associations with demographic and laboratory parameters.
Main Results:
- A moderate correlation was observed between sUMOD and uUMOD, adjusted for eGFR (r = 0.27).
- eGFR showed a stronger correlation with sUMOD (r = 0.44) than with uUMOD (r = 0.21).
- Independently, sUMOD was associated with eGFR, C-reactive protein, and male sex. uUMOD was associated with male sex, diabetes, and hypertension, with differing directions of association.
Conclusions:
- Serum uromodulin (sUMOD) demonstrates a stronger association with kidney function (eGFR) compared to urine uromodulin (uUMOD).
- The distinct correlates of sUMOD and uUMOD suggest differential regulation of their apical and basolateral secretion pathways.
- These findings highlight the potential of sUMOD and uUMOD as differential biomarkers in renal and cardiovascular health.
Abstract:
Uromodulin is released into serum (sUMOD) and urine (uUMOD) exclusively by renal tubular cells. Both sUMOD and uUMOD are correlated with estimated glomerular filtration rate (eGFR), and associated with mortality and cardiovascular disease (CVD). However, no study to our knowledge has measured both sUMOD and uUMOD in the same population, thus the relationship of sUMOD with uUMOD with one another, and their respective correlates have not been evaluated simultaneously. We evaluated the correlations of sUMOD, uUMOD with eGFR in a random sub-cohort (n = 933) of the Cardiovascular Health Study and their associations with demographic and laboratory parameters and CVD risk factors using multi-variable linear regression analysis. The mean age of the cohort was 78 years, 40% were male and 15% were Black. The mean sUMOD level was 127 ng/mL, uUMOD was 30 500 ng/mL and eGFR was 63 mL/min/1.73 m2 . Correlation between sUMOD and uUMOD, adjusted for eGFR was moderate (r = 0.27 [95% confidence interval = 0.21-0.33]). The correlation of eGFR with sUMOD (r = 0.44 [0.39-0.49]) was stronger than with uUMOD (r = 0.21 [0.15-0.27]). In multi-variable analysis adjusting sUMOD for uUMOD and vice versa, sUMOD was independently associated with eGFR (β = 1.3 [1.1-1.6]), log2 C-reactive protein (β = -4.2 [-6.8 to -1.6]) and male sex (β = -13.6 [-22.7 to -4.5]). In contrast, male sex was associated with higher uUMOD (β = 3700 [400-7000]), while diabetes (β = -6400 [-10 600 to -2100]) and hypertension (-4300 [-7500 to -1100]) were associated with lower uUMOD levels. We conclude that sUMOD is more strongly associated with eGFR compared with uUMOD. Correlates of sUMOD and uUMOD differ substantially, suggesting that apical and basolateral secretion may be differentially regulated.
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