Department of Pediatrics, Section of Pediatric Nephrology, Yale University, New Haven, CT (C.Y.B., J.H.G.).
Bloomberg School of Public Health, John Hopkins University, Baltimore, MD (M.B.M.).
Hypertension. 2022 Oct;79(10):2298-2304. doi: 10.1161/HYPERTENSIONAHA.122.19566. Epub 2022 Aug 3.
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.
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.
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 m (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 (>0.05 in all models).
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.
尿调蛋白调节 Henle 袢中的钠-钾-二氯转运体的活性。在成年人中,尿液中尿调蛋白水平升高与盐摄入后血压(BP)升高幅度增大有关。我们假设在患有慢性肾脏病的儿童中,尿液中尿调蛋白水平升高与 BP 升高相关,且饮食钠对此关联存在交互作用。
在儿童慢性肾脏病队列中,我们利用单变量和多变量线性回归模型来评估基线点尿尿调蛋白水平与尿肌酐(Umod/Cr mg/g)的比值与 24 小时平均收缩压和舒张压以及基线诊室血压之间的关系。我们还测试了钠摄入量(g/天)是否改变了这些关系。
在 436 名参与者中,中位年龄为 12.4 岁(8.9-15.2),中位估计肾小球滤过率为 50 mL/min/1.73 m(36-62),中位 24 小时平均收缩压为 112 mm Hg(104-119)。慢性肾脏病的病因是肾小球疾病占 27%。在单变量模型中,Umod/Cr 比值每增加 2 倍,与 24 小时平均收缩压降低 1.66 mm Hg(95%CI,-2.31 至 -1.00)和诊室收缩压降低 1.71 mm Hg(-2.45 至 -0.97)相关。然而,在多变量模型中,Umod/Cr 与 24 小时或诊室 BP 之间均无统计学显著关联。我们未发现尿调蛋白与钠摄入量之间在其对 BP 的影响上存在显著交互作用(所有模型中均>0.05)。
尿液尿调蛋白水平与儿童慢性肾脏病队列中的 BP 无关。需要进一步的研究来在健康的儿科队列中证实这一发现。