Renal tubulointerstitial fibrosis caused by congenital ureteropelvic junction obstruction (UPJO) may lead to the development of obstructive nephropathy (ON) and the impairment of kidney function. Hence, the identification of early biomarkers of this condition might be of assistance in therapeutic decisions. This study evaluates serum and urinary metalloproteinases MMP-1, MMP-2, and MMP-9 and tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2 as potential biomarkers of ON in children with congenital unilateral hydronephrosis (HN) caused by UPJO. Forty-five (45) children with congenital HN of different grades of severity and twenty-one (21) healthy controls were enrolled in the study. Urinary and serum concentrations of MMP-1, MMP-2, MMP-9, TIMP-1 and TIMP-2 were measured using specific ELISA kits. The urinary excretions were expressed as biomarker/creatinine (Cr) ratios. To evaluate the extracellular matrix remodelling process activity, the serum and urinary MMP-1, -2, -9/TIMP-1, -2 ratios were also calculated. In comparison with the controls, patients with HN, independent of the grade, showed significantly increased median serum MMP-9, TIMP-1, and TIMP-2, median urinary MMP-9/Cr, and TIMP-2/Cr ratios. Lower median values of serum MMP-2/TIMP-1, MMP-9/TIMP-1 in patients with HN were also revealed. Additionally, higher urinary MMP-2/Cr, lower urinary MMP-2/TIMP-2, and lower serum MMP-9/TIMP-2 ratios were observed in patients with HN grades 3 and 4. Patients with ON diagnosed by renal scintigraphy had a significantly higher median serum MMP-9 concentration and lower median serum MMP-9/TIMP-1, -2 ratios in comparison with those without this condition. Patients with nonglomerular proteinuria had a significantly higher median serum TIMP-1 concentration, a higher median urinary TIMP-2/Cr ratio, and a lower serum MMP-9/TIMP-1 ratio compared to those without this symptom. The relationship between the measured biomarkers and the relative function of the obstructed kidney showed no correlations. The ROC curve analysis showed a promising diagnostic profile for the detection of ON for serum MMP-9 and the serum MMP-9/TIMP-1 and MMP-9/TIMP-2 ratios. In conclusion, the results of this study suggest that patients with HN, particularly with grades 3 and 4, are at higher risk of renal tubulointerstitial fibrosis. The noninvasive markers of this condition considered are urinary MMP-2/Cr and MMP-9/Cr, serum MMP-9, serum and urinary MMP-2, MMP-9/TIMP-1, -2. Additionally, serum MMP-9 and MMP-9/TIMP-1, -2 may become promising markers of ON.

中文翻译：

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选定的金属基质金属蛋白酶和金属蛋白酶组织抑制剂作为单侧肾积水患儿肾小管间质纤维化的潜在生物标志物。

先天性输尿管盆腔连接阻塞（UPJO）引起的肾小管间质纤维化可能导致阻塞性肾病（ON）的发展和肾功能的损害。因此，这种情况的早期生物标志物的识别可能有助于治疗决策。这项研究评估了血清和尿液中的金属蛋白酶MMP-1，MMP-2和MMP-9以及金属蛋白酶TIMP-1和TIMP-2的组织抑制剂作为UPJO引起的先天性单侧肾积水（HN）患儿ON的潜在生物标志物。这项研究纳入了四十五（45）名不同严重程度的先天性HN儿童和二十一（21）名健康对照者。使用特定的ELISA试剂盒测量MMP-1，MMP-2，MMP-9，TIMP-1和TIMP-2的尿液和血清浓度。尿液排泄物以生物标志物/肌酐（Cr）之比表示。为了评估细胞外基质重塑过程的活性，还计算了血清和尿中MMP-1，-2，-9 / TIMP-1，-2的比率。与对照组相比，患有HN的患者，与年级无关，显示血清MMP-9，TIMP-1和TIMP-2的中位数，尿中MMP-9 / Cr和TIMP-2 / Cr的中位数显着增加。HN患者血清MMP-2 / TIMP-1，MMP-9 / TIMP-1的中位数也较低。此外，在HN 3和4级患者中观察到较高的尿MMP-2 / Cr，较低的尿MMP-2 / TIMP-2和较低的血清MMP-9 / TIMP-2比率。血清MMP-9的中位数浓度显着较高，而血清MMP-9 / TIMP-1的中位数较低，与没有这种情况的比率相比为-2的比率。与无此症状的患者相比，患有非肾小球蛋白尿症的患者的血清TIMP-1浓度中位数显着较高，尿中TIMP-2 / Cr的中位数较高，血清MMP-9 / TIMP-1的比率较低。测得的生物标志物与阻塞性肾脏的相对功能之间没有关系。ROC曲线分析显示了用于检测血清MMP-9的ON以及血清MMP-9 / TIMP-1和MMP-9 / TIMP-2比率的诊断前景。总之，这项研究的结果表明，患有HN的患者，尤其是3级和4级的患者，肾小管间质纤维化的风险更高。考虑到的这种情况的非侵入性标志物是尿MMP-2 / Cr和MMP-9 / Cr，血清MMP-9，血清和尿MMP-2，MMP-9 / TIMP-1，-2。另外，血清MMP-9和MMP-9 / TIMP-1，-2可能成为ON的有希望的标志。