Pediatric Urology Division, Pediatric Surgery Department at Nationwide Children's Hospital, Columbus, OH, USA; Center for Clinical and Translational Research at the Research Institute of Nationwide Children's Hospital, Columbus, OH, USA.
Center for Clinical and Translational Research at the Research Institute of Nationwide Children's Hospital, Columbus, OH, USA; Pediatric Nephrology Division, Pediatric Department at Nationwide Children's Hospital, Columbus, OH, USA.
J Pediatr Urol. 2018 Jun;14(3):238.e1-238.e6. doi: 10.1016/j.jpurol.2018.03.006. Epub 2018 Mar 29.
Antimicrobial peptides (AMPs) have historically been evaluated for their role in protecting against uropathogens. However, there is mounting evidence to support their expression in noninfectious injury, with unclear meaning as to their function. It is possible that AMPs represent urothelial injury. Urinary tract obstruction is known to alter the urothelium; however, AMPs have not been evaluated for expression in this noninfectious injury.
A pilot study to compare urinary AMP expression in children undergoing surgical intervention for ureteropelvic junction obstruction (UPJO) with nonobstructed controls.
Bladder urine was collected from consenting/assenting pediatric patients with UPJO at intervention. Control bladder urines were obtained from age-matched and sex-matched healthy children without known obstruction or infection. Enzyme-linked immunosorbent assays were run for the following AMPs: β defense 1 (BD-1), neutrophil gelatinase-associated lipocalin (NGAL), cathelicidin (LL-37), hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), and human α defensin 5 (HD-5); and normalized to urine creatinine. Results were analyzed with Student's t-test or Mann-Whitney U test, when appropriate, and receiver operating characteristic curves. A P-value of <0.05 was considered significant.
Thirty bladder urine samples were obtained from children with UPJO at the time of decompressive intervention. Mean patient age was 4.7 years (range 0.3-18.4); 20 (67%) patients were male. Fifteen bladder urine samples were obtained from age-matched and sex-matched controls. Urinary AMP levels were significantly higher in UPJO patients than controls for BD-1 (P = 0.015), NGAL (P < 0.001), LL-37 (P < 0.001), and HIP/PAP (P = 0.046). Optimal threshold values of these AMPs were determined, with each demonstrating significant odds ratios of predicting urinary obstruction.
Certain urinary AMPs are altered even in noninfectious urinary tract pathology. This represents a novel induction of AMP expression, as the current study is the first to report elevations in BD-1 and HIP/PAP in urinary tract obstruction. This suggests other roles for these AMPs outside of their antimicrobial properties, and likely is a reflection of the urothelial and tubular stress resulting from obstructive uropathy.
Induction of AMPs BD-1, NGAL, LL-37, and HIP/PAP was found to occur in urinary tract obstruction. Further evaluation of AMP expression as a biomarker of uroepithelial injury outside of infection is indicated.
抗菌肽（AMPs）在历史上一直被评估用于保护尿路病原体。然而，越来越多的证据支持它们在非传染性损伤中的表达，但其功能尚不清楚。AMP 可能代表尿路上皮损伤。已知尿路梗阻会改变尿路上皮；然而，尚未评估 AMP 在这种非传染性损伤中的表达。
比较接受肾盂输尿管连接部梗阻（UPJO）手术干预的儿童和无梗阻对照者的尿 AMP 表达。
在干预时从同意/同意的 UPJO 患儿的膀胱尿液中收集。对照膀胱尿液取自年龄和性别匹配的无已知梗阻或感染的健康儿童。运行酶联免疫吸附测定法（ELISA）用于以下 AMPs：β防御素 1（BD-1）、中性粒细胞明胶酶相关脂质运载蛋白（NGAL）、cathelicidin（LL-37）、肝癌-肠-胰腺/胰腺炎相关蛋白（HIP/PAP）和人α防御素 5（HD-5）；并标准化为尿肌酐。使用 Student's t 检验或 Mann-Whitney U 检验（视情况而定）和接收者操作特征曲线进行分析。P 值<0.05 被认为具有统计学意义。
在减压干预时，从 30 名 UPJO 患儿的膀胱尿液中获得尿液样本。患儿的平均年龄为 4.7 岁（范围 0.3-18.4）；20 名（67%）患儿为男性。从年龄和性别匹配的对照中获得 15 个膀胱尿液样本。与对照组相比，UPJO 患者的尿 AMP 水平明显升高，BD-1（P=0.015）、NGAL（P<0.001）、LL-37（P<0.001）和 HIP/PAP（P=0.046）。确定了这些 AMP 的最佳阈值值，每个 AMP 均显示出预测尿路梗阻的显著优势比。
某些尿 AMP 即使在非感染性尿路病理中也会发生改变。这代表着 AMP 表达的一种新诱导，因为目前的研究是首次报告 BD-1 和 HIP/PAP 在尿路梗阻中升高。这表明这些 AMP 除了具有抗菌特性外，可能还有其他作用，这可能反映了梗阻性尿路病导致的尿路上皮和肾小管应激。
发现尿 AMPs BD-1、NGAL、LL-37 和 HIP/PAP 的诱导发生在尿路梗阻中。需要进一步评估 AMP 作为感染以外的尿上皮损伤的生物标志物的表达。
