Background

Children with congenital anomalies of kidney and urinary tract (CAKUT) are at high risk of progressive deterioration of kidney function and further developing stage 5 chronic kidney disease (CKD 5), even after a successful surgery. This prospective study was designed to determine whether urinary biomarkers can predict progressive deterioration of kidney function in children with CAKUT.

Methods

The study included 50 consecutive children, aged < 14 years, who were diagnosed with congenital uropathies (PUV, VUR, and PUJO) and 20 age-matched controls. Examination of four urinary biomarkers, i.e., trefoil family factors (TFF) 1 and 3, neutrophil gelatinase–associated lipocalin (NGAL) and microalbuminuria (MALB) was done at the beginning of follow-up. Kidney function was assessed, at the beginning and after 12-months of follow-up, by technetium-99m diethylene triamine pentaacetic acid (DTPA) and technetium-99m dimercaptosuccinic acid (DMSA) scans. Progressive deterioration in the kidney function was defined as a fall in the GFR from ≥ 60 to < 60 ml/min/1.73 m² on comparing the baseline and latest DTPA scans; and/or new-onset cortical scar/scars or increase in the size of previous scar/scars on serial DMSA scans. Group 1 and group 2 included children without and with progressive functional deterioration respectively.

Results

The median (IQR) age of children with CAKUT and controls was 3 (1.5–5) and 2.3 (1.2–3.6) years, respectively, and showed no significant difference (p = 0.29). Median concentrations of TFF1, TFF3, NGAL, and microalbumin in patients were 44.5, 176.5, 281.2, and 15.5 mcg/gCr, respectively, and were significantly elevated as compared to controls (p < 0.05). Children belonging to group 2 had significantly higher concentration of biomarkers as compared to those in group 1. TFF3 was found have the highest AUC (0.9198) on ROC curve for predicting progressive functional deterioration.

Conclusion

Urinary TFFs, NGAL, and microalbumin significantly correlate with progressive deterioration of kidney function in children harboring CAKUT. TFF3, with the strongest prediction of functional deterioration, is an emerging peptide showing sufficient potential to be included in the biomarker panel.

中文翻译：

---

尿液生物标志物作为床旁检测，用于预测先天性肾脏和泌尿道异常肾功能进行性恶化：三叶家族因子 (TFF) 作为新兴生物标志物

背景

患有先天性肾脏和泌尿道异常 (CAKUT) 的儿童即使在成功手术后也面临肾功能进行性恶化和进一步发展为 5 期慢性肾病 (CKD 5) 的高风险。这项前瞻性研究旨在确定尿液生物标志物是否可以预测 CAKUT 儿童肾功能的进行性恶化。

方法

该研究包括 50 名年龄 < 14 岁、被诊断为先天性尿路疾病（PUV、VUR 和 PUJO）的儿童和 20 名年龄匹配的对照。在随访开始时检查了四种尿液生物标志物，即三叶家族因子 (TFF) 1 和 3、中性粒细胞明胶酶相关载脂蛋白 (NGAL) 和微量白蛋白尿 (MALB)。在开始和 12 个月的随访后，通过锝 99m 二亚乙基三胺五乙酸 (DTPA) 和锝 99m 二巯基丁二酸 (DMSA) 扫描评估肾功能。肾功能进行性恶化定义为 GFR 从 ≥ 60 降至 < 60 ml/min/1.73 m ²比较基线和最新的 DTPA 扫描；和/或新发作的皮质疤痕/疤痕或在串行 DMSA 扫描中先前疤痕/疤痕的大小增加。第 1 组和第 2 组分别包括没有和有进行性功能恶化的儿童。

结果

CAKUT 和对照组儿童的中位 (IQR) 年龄分别为 3 (1.5-5) 和 2.3 (1.2-3.6) 岁，差异无显着性 ( p = 0.29)。患者 TFF1、TFF3、NGAL 和微量白蛋白的中位浓度分别为 44.5、176.5、281.2 和 15.5 mcg/gCr，与对照组相比显着升高（p < 0.05）。与第 1 组相比，第 2 组儿童的生物标志物浓度明显更高。发现 TFF3 在 ROC 曲线上具有最高的 AUC (0.9198)，可预测进行性功能恶化。

结论

尿 TFF、NGAL 和微量白蛋白与患有 CAKUT 的儿童的肾功能进行性恶化显着相关。TFF3 对功能恶化的预测最强，是一种新兴的肽，显示出足够的潜力被纳入生物标志物组。