关键词: 先天性肾脏及尿路畸形, 血管紧张素转换酶2, 配对盒基因2, 急性肾损伤, 生物标志物

Abstract:

Objective To investigate the expression levels of urinary ACE2 and PAX2 proteins in children with congenital anomalies of the kidney and urinary tract （CAKUT） and their association with acute kidney injury （AKI）， and to assess the diagnostic value of these proteins as biomarkers for early renal injury in CAKUT. Methods A total of 266 children aged 1 ~ 18 years with CAKUT were enrolled. They were divided into the CAKUT with AKI group （n = 68） and the CAKUT without AKI group （n = 198） in accordance with the Kidney Disease： Improving Global Outcomes （KDIGO） criteria， along with a matched healthy control group （n = 45）. The levels of angiotensin-converting enzyme 2 （ACE2） and paired box 2 （PAX2） in morning urine were measured by means of enzyme-linked immunosorbent assay （ELISA）. Statistical analysis was carried out in combination with renal function indicators such as serum creatinine and estimated glomerular filtration rate （eGFR）. The diagnostic efficacy was assessed via receiver operating characteristic （ROC） curve analysis， and the correlation between the markers and eGFR was investigated using Pearson correlation analysis. Results The levels of urinary ACE2 and PAX2 in the CAKUT-AKI group were significantly higher compared to those in the non - AKI group and the healthy group， and they exhibited a stepwise increase as the AKI stages progressed （P < 0.01）. There was no statistically significant difference between the non - AKI group and the healthy group （P > 0.05）. Both ACE2 and PAX2 demonstrated strong negative correlations with eGFR （r = -0.72， P < 0.01； r = -0.805， P < 0.01）. The area under the curve （AUC） for ACE2 alone in diagnosis was 0.917 （cut-off value 177.8 ng/mg Cr， sensitivity 80.9%， specificity 86.4%）； the AUC for PAX2 alone in diagnosis was 0.853 （cut-off value 11.1 pg/mg Cr， sensitivity 80.3%， specificity 76.1%）； the combined testing AUC increased to 0.956 （sensitivity 88.2%， specificity 87.9%）， which was significantly superior to single indicators （P < 0.01）. Conclusion Urinary ACE2 and PAX2 can be utilized to aid in the diagnosis of CAKUT complicated by acute kidney injury， demonstrating favorable diagnostic efficacy.

Key words: congenital anomalies of the kidney and urinary tract, angiotensin-converting enzyme 2, paired box gene 2, acute kidney injury, biomarkers