Clinic of Pediatrics, Institute of Clinical Medicine, Faculty of Medicine, Vilnius University, Vilnius, Lithuania.
Department of Internal Medicine/Nephrology, University of Michigan, Ann Arbor, Michigan, USA; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA.
Kidney Int. 2019 Jul;96(1):214-221. doi: 10.1016/j.kint.2019.01.035. Epub 2019 Mar 20.
Urinary epidermal growth factor (uEGF) has recently been identified as a promising biomarker of chronic kidney disease (CKD) progression in adults with glomerular disease. Low levels of uEGF predict CKD progression and appear to reflect the extent of tubulointerstitial damage. We investigated the relevance of uEGF in pediatric CKD. We performed a post hoc analysis of the Cardiovascular Comorbidity in Children with CKD (4C) study, which prospectively follows children aged 6-17 years with baseline estimated glomerular filtration rate (eGFR) of 10-60 ml/min/1.73 m. uEGF levels were measured in archived urine collected within 6 months of enrollment. Congenital abnormalities of the kidney and urinary tract were the most common cause of CKD, with glomerular diseases accounting for <10% of cases. Median eGFR at baseline was 28 ml/min/1.73 m, and 288 of 623 participants (46.3%) reached the composite endpoint of CKD progression (50% eGFR loss, eGFR < 10 ml/min/1.73 m, or initiation of renal replacement therapy). In a Cox proportional hazards model, higher uEGF/Cr was associated with a decreased risk of CKD progression (HR 0.76; 95% CI 0.69-0.84) independent of age, sex, baseline eGFR, primary kidney disease, proteinuria, and systolic blood pressure. The addition of uEGF/Cr to a model containing these variables resulted in a significant improvement in C-statistics, indicating better prediction of the 1-, 2- and 3-year risk of CKD progression. External validation in a prospective cohort of 222 children with CKD demonstrated comparable results. Thus, uEGF may be a useful biomarker to predict CKD progression in children with CKD.
尿表皮生长因子 (uEGF) 最近被确定为成人肾小球疾病慢性肾脏病 (CKD) 进展的有前途的生物标志物。uEGF 水平低预测 CKD 进展，似乎反映了肾小管间质损伤的程度。我们研究了 uEGF 在儿科 CKD 中的相关性。我们对前瞻性随访肾小球滤过率 (eGFR) 为 10-60ml/min/1.73m 的 6-17 岁儿童的“CKD 患儿心血管合并症（4C）研究”进行了事后分析。uEGF 水平在入组后 6 个月内采集的存档尿液中进行了测量。肾脏和泌尿道先天异常是 CKD 的最常见原因，肾小球疾病占<10%的病例。基线时 eGFR 的中位数为 28ml/min/1.73m，623 名参与者中有 288 名（46.3%）达到 CKD 进展的复合终点（eGFR 损失 50%，eGFR<10ml/min/1.73m 或开始肾脏替代治疗）。在 Cox 比例风险模型中，较高的 uEGF/Cr 与 CKD 进展风险降低相关（HR 0.76；95%CI 0.69-0.84），与年龄、性别、基线 eGFR、原发性肾脏疾病、蛋白尿和收缩压无关。在包含这些变量的模型中加入 uEGF/Cr 可显著提高 C 统计量，表明可更好地预测 1 年、2 年和 3 年 CKD 进展的风险。在 222 名 CKD 儿童的前瞻性队列中进行的外部验证也得出了类似的结果。因此，uEGF 可能是预测 CKD 进展的有用生物标志物。
