McLeod Daryl J, Sebastião Yuri V, Ching Christina B, Greenberg Jason H, Furth Susan L, Becknell Brian
Section of Urology, Nationwide Children's Hospital, Columbus, OH, 43205, USA.
Center for Surgical Outcomes Research, Nationwide Children's Hospital, Columbus, OH, 43205, USA.
Pediatr Nephrol. 2020 Oct;35(10):1907-1914. doi: 10.1007/s00467-020-04602-7. Epub 2020 May 22.
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.
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.
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).
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.
先天性梗阻性尿路病（OU）是小儿肾衰竭的主要原因，代表一种独特的损伤机制，部分源于肾小管扩张和缺血。肾小管损伤生物标志物有可能改善OU特异性风险分层。
在儿童慢性肾脏病（CKiD）研究中识别出OU患者。“病例”定义为接受任何肾脏替代治疗（KRT）的个体，而“对照”为年龄和研究时间匹配且在最后一次研究访视时未接受KRT的个体。在入组时和每年测量尿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。尿值以尿肌酐进行标准化。
共识别出22例病例和22例对照，基线和随访时的中位（四分位间距）年龄分别为10.5（9.0 - 13.0）岁和15.9（13.9 - 16.9）岁。入组时，所测量的任何尿（u）或血浆（p）生物标志物在病例和对照之间均未发现差异。然而，在整个研究期间，病例组的平均pNGAL和uL-FABP/肌酐升高（分别为每年15.38 ng/ml和每年0.20 ng/ml per mg/dl，两者p均 = 0.01），而对照组保持稳定。在控制基线肾小球滤过率（GFR）后，这种情况仍然持续。
在OU患儿中，pNGAL和uL-FABP水平在接受KRT前的5年中升高；独立于基线GFR。未来研究有必要确定最佳临界值，并确定这些标志物是否优于当前临床预测指标。
