BACKGROUND Congenital obstructive uropathy (OU) is a leading cause of pediatric kidney failure, representing a unique mechanism of injury, in part from renal tubular stretch and ischemia. Tubular injury biomarkers have potential to improve OU-specific risk stratification. METHODS Patients with OU were identified in the Chronic Kidney Disease in Children (CKiD) study. "Cases" were defined as individuals receiving any kidney replacement therapy (KRT), while "controls" were age- and time-on-study matched and KRT free at last study visit. Urine and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) levels were measured at enrollment and annually and compared between cases and controls. Urine values were normalized to urine creatinine. RESULTS In total, 22 cases and 22 controls were identified, with median (interquartile range) ages of 10.5 (9.0-13.0) and 15.9 (13.9-16.9) years at baseline and outcome, respectively. At enrollment there were no differences noted between cases and controls for any urine (u) or plasma (p) biomarker measured. However, the mean pNGAL and uL-FABP/creatinine increased throughout the study period in cases (15.38 ng/ml per year and 0.20 ng/ml per mg/dl per year, respectively, p = 0.01 for both) but remained stable in controls. This remained constant after controlling for baseline glomerular filtration rate (GFR). CONCLUSIONS In children with OU, pNGAL and uL-FABP levels increased over the 5 years preceding KRT; independent of baseline GFR. Future studies are necessary to identify optimal cutoff values and to determine if these markers outperform current clinical predictors.

中文翻译：

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梗阻性尿路病儿童的纵向肾损伤生物标志物轨迹。


背景先天性梗阻性尿病（OU）是小儿肾衰竭的主要原因，代表了一种独特的损伤机制，部分原因是肾小管拉伸和缺血。肾小管损伤生物标志物有可能改善 OU 特定的风险分层。方法 OU 患者是在儿童慢性肾脏病 (CKiD) 研究中确定的。 “病例”被定义为接受任何肾脏替代疗法（KRT）的个体，而“对照”则为年龄和研究时间匹配且在上次研究访视时未接受 KRT 的个体。在入组时和每年测量尿液和血浆中性粒细胞明胶酶相关脂质运载蛋白 (NGAL)、白细胞介素 18 (IL-18) 和肝型脂肪酸结合蛋白 (L-FABP) 水平，并在病例和对照之间进行比较。将尿值标准化为尿肌酐。结果 总共确定了 22 例病例和 22 例对照，基线和结果时的中位（四分位距）年龄分别为 10.5（9.0-13.0）岁和 15.9（13.9-16.9）岁。入组时，病例和对照之间测量的任何尿液 (u) 或血浆 (p) 生物标志物均未发现差异。然而，在整个研究期间，病例的平均 pNGAL 和 uL-FABP/肌酐有所增加（分别为每年 15.38 ng/ml 和每年每 mg/dl 0.20 ng/ml，p = 0.01），但在对照组中保持稳定。在控制基线肾小球滤过率（GFR）后，该值保持不变。结论 在 OU 儿童中，pNGAL 和 uL-FABP 水平在 KRT 之前的 5 年内有所增加；独立于基线 GFR。未来的研究有必要确定最佳截止值并确定这些标志物是否优于当前的临床预测因子。