Clinical and Translational Research Accelerator, Yale University, New Haven, CT, USA.
Bloomberg School of Public Health, John Hopkins University, Baltimore, MD, USA.
Pediatr Nephrol. 2023 Nov;38(11):3859-3862. doi: 10.1007/s00467-023-05947-5. Epub 2023 Mar 29.
Uromodulin is the most abundant protein in the urine of healthy adults, and higher urine concentrations mark better tubular health. Greater kidney size and function are predictors of higher uromodulin levels in adults. Urine uromodulin has not yet been studied in children with chronic kidney disease (CKD). Thus, we sought to determine the relationship between age and kidney function with urine uromodulin levels in children with CKD.
In the CKD in Children (CKiD) cohort, we utilized multivariable linear regression to evaluate the relationship of age and eGFR with urine uromodulin levels. The primary outcome was uromodulin indexed to urine creatinine (Umod/Cr, mg/g), which was log-transformed given its skewed distribution.
Among 677 CKiD participants, the median age was 11.8 years (8.2-15.3), the median eGFR was 49 ml/min/1.73 m (37-63), the etiology of CKD was glomerular disease in 31%, and the median Umod/Cr level was 0.114 mg/g (0.045-0.226). In the multivariable models, each one-year older age was associated with 0.18 (12%) lower log(Umod/Cr) and 0.20 (13%) lower log(Umod/Cr) among those with non-glomerular and glomerular disease, respectively (p < 0.001). However, we did not find a statistically significant association between eGFR and Umod/Cr in either participants with non-glomerular or glomerular disease (p = 0.13 and p = 0.58, respectively).
Among children with CKD, older age is significantly associated with lower Umod/Cr, independent of eGFR. Further studies are needed to comprehensively evaluate age-specific reference ranges for urine uromodulin and to evaluate the longitudinal relationship of uromodulin with both age and eGFR in children with CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.
尿调蛋白是健康成年人尿液中含量最丰富的蛋白质,尿液中浓度越高表明肾小管健康状况越好。更大的肾脏体积和功能是成人尿调蛋白水平升高的预测因素。尿调蛋白尚未在患有慢性肾脏病 (CKD) 的儿童中进行研究。因此,我们旨在确定年龄和肾功能与 CKD 儿童尿调蛋白水平之间的关系。
在 CKD 儿童(CKiD)队列中,我们利用多变量线性回归来评估年龄和 eGFR 与尿调蛋白水平的关系。主要结局指标是尿调蛋白与尿肌酐的比值(Umod/Cr,mg/g),由于其偏态分布,对其进行了对数转换。
在 677 名 CKiD 参与者中,中位年龄为 11.8 岁(8.2-15.3),中位 eGFR 为 49 ml/min/1.73 m (37-63),CKD 的病因在 31%的参与者中为肾小球疾病,中位 Umod/Cr 水平为 0.114 mg/g(0.045-0.226)。在多变量模型中,与非肾小球疾病和肾小球疾病参与者相比,年龄每增加 1 岁,log(Umod/Cr)分别降低 0.18(12%)和 0.20(13%)(p<0.001)。然而,我们没有发现 eGFR 与非肾小球疾病或肾小球疾病参与者的 Umod/Cr 之间存在统计学显著关联(p=0.13 和 p=0.58)。
在患有 CKD 的儿童中,年龄与 Umod/Cr 呈显著负相关,与 eGFR 无关。需要进一步的研究来全面评估尿调蛋白的年龄特异性参考范围,并评估尿调蛋白与年龄和 eGFR 在 CKD 儿童中的纵向关系。可在补充信息中查看图形摘要的更高分辨率版本。