Christine Y Bakhoum1, Matthew B Matheson2, Jason H Greenberg1, Susan L Furth3, Joachim H Ix4, Pranav S Garimella5. 1. Department of Pediatrics, Section of Pediatric Nephrology, Yale University, New Haven, CT (C.Y.B., J.H.G.). 2. Bloomberg School of Public Health, John Hopkins University, Baltimore, MD (M.B.M.). 3. Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania and Division of Nephrology, Children's Hospital of Philadelphia (S.L.F.). 4. Nephrology Section, Medicine Service, Veterans Affairs San Diego Healthcare System, La Jolla, CA (J.H.I.). 5. Division of Nephrology and Hypertension, Department of Medicine, University of California San Diego, La Jolla (J.H.I., P.S.G.).
Abstract
BACKGROUND: Uromodulin regulates activity of the sodium-potassium-two-chloride transporter in the loop of Henle. In adults, higher urine uromodulin levels are associated with greater rise in blood pressure (BP) in response to salt intake. We hypothesized that higher urine uromodulin levels would be associated with higher BP in children with chronic kidney disease, and that there would be an interaction of dietary sodium on this association. METHODS: In the chronic kidney disease in children Cohort, we utilized univariable and multivariable linear regression models to evaluate the relationship between baseline spot urine uromodulin levels indexed to urine creatinine (Umod/Cr mg/g) and 24-hour mean systolic and diastolic BP, as well as baseline clinic BP. We also tested whether sodium intake (g/day) modified these relationships. RESULTS: Among 436 participants, the median age was 12.4 years (8.9-15.2), median estimated glomerular filtration rate was 50 mL/min per 1.73 m2 (36-62), and median 24-hour mean systolic BP was 112 mm Hg (104-119). The etiology of chronic kidney disease was glomerular disease in 27%. In univariable models, each 2-fold higher Umod/Cr ratio was associated with a 1.66 mm Hg (95% CI, -2.31 to -1.00) lower 24-hour mean systolic and a 1.71 mm Hg (-2.45 to -0.97) lower clinic systolic BP. However, there was no statistically significant association between Umod/Cr and either 24-hour or clinic BP in multivariable models. We did not find a significant interaction between uromodulin and sodium intake in their effect on BP (P>0.05 in all models). CONCLUSIONS: Urine uromodulin levels are not associated with BP in the chronic kidney disease in children cohort. Further studies are needed to confirm this finding in healthy pediatric cohorts.
BACKGROUND: Uromodulin regulates activity of the sodium-potassium-two-chloride transporter in the loop of Henle. In adults, higher urine uromodulin levels are associated with greater rise in blood pressure (BP) in response to salt intake. We hypothesized that higher urine uromodulin levels would be associated with higher BP in children with chronic kidney disease, and that there would be an interaction of dietary sodium on this association. METHODS: In the chronic kidney disease in children Cohort, we utilized univariable and multivariable linear regression models to evaluate the relationship between baseline spot urine uromodulin levels indexed to urine creatinine (Umod/Cr mg/g) and 24-hour mean systolic and diastolic BP, as well as baseline clinic BP. We also tested whether sodium intake (g/day) modified these relationships. RESULTS: Among 436 participants, the median age was 12.4 years (8.9-15.2), median estimated glomerular filtration rate was 50 mL/min per 1.73 m2 (36-62), and median 24-hour mean systolic BP was 112 mm Hg (104-119). The etiology of chronic kidney disease was glomerular disease in 27%. In univariable models, each 2-fold higher Umod/Cr ratio was associated with a 1.66 mm Hg (95% CI, -2.31 to -1.00) lower 24-hour mean systolic and a 1.71 mm Hg (-2.45 to -0.97) lower clinic systolic BP. However, there was no statistically significant association between Umod/Cr and either 24-hour or clinic BP in multivariable models. We did not find a significant interaction between uromodulin and sodium intake in their effect on BP (P>0.05 in all models). CONCLUSIONS: Urine uromodulin levels are not associated with BP in the chronic kidney disease in children cohort. Further studies are needed to confirm this finding in healthy pediatric cohorts.
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