İnözü Mihriban, Büyükyılmaz Gönül, Avcı Begüm, Aygar İsmail Selçuk, Çaycı Fatma Semsa, Uçaktürk Seyit Ahmet, Mengen Eda, Özlü Sare Gülfem, Bayrakçı Umut Selda
Department of Pediatric Nephrology, Ankara City Hospital, Ankara, Turkey.
Faculty of Medicine, Department of Pediatric Nephrology, Ankara Yıldırım Beyazıt University, Ankara, Turkey.
Eur J Pediatr. 2025 Jun 27;184(7):451. doi: 10.1007/s00431-025-06278-3.
This study aims to determine the role of urinary plasminogen, a serine protease that reflects damage to the glomerular filtration barrier, in the early detection of diabetic kidney disease in pediatric patients with type 1 diabetes mellitus (T1DM). Pediatric patients, who had been followed up with T1DM for at least 2 years, and healthy matched controls were included. The association between urine plasminogen (uPlasminogen) levels and urine plasminogen-to-creatinine ratio (uPlgCR) with urine albumin-to-creatinine ratio (uACR) was examined, as well as determining a cut-off value for uPlasminogen to predict microalbuminuria. A total of 56 T1DM patients and 30 healthy matched controls were included. There was no significant difference in eGFR (estimated glomerular filtration rate) and systolic and diastolic blood pressure between the groups. uPlasminogen level was determined to be higher in the albuminuric group than control (p = 0.001) and uPlgCR was higher in the normoalbuminuric and albuminuric groups than control (p = 0.004, p = 0.002, respectively). There was a weak positive correlation between uPlasminogen and uPlgCR with uACR (r 0.38, p = 0.004; r 0.28, p = 0.03, respectively). The diagnostic performance of uPlasminogen in predicting albuminuria was evaluated by ROC-curve analysis, showing an AUC of 0.69 (p = 0.02; 95% CI [0.521-0.861]), with a sensitivity of 75% and specificity of 65.5% at a cut-off value of 7.1 µg/L.
A positive correlation was found between uPlasminogen and uPlgCR with albuminuria. Also, uPlasminogen was determined to predict albuminuria. Most importantly, uPlgCR was elevated in diabetic patients before albuminuria developed. uPlgCR may serve as a potential early marker or therapeutic target of DKD, pending further longitudinal validation.
• Urinary plasminogen correlates with albuminuria in diabetic patients.
• Urinary plasminogen and uPlgCR levels exhibited a significant and positive correlation with uACR. The new findings in this study are that uPlgCR was detected in urine before microalbuminuria develops, and that uPlasminogen predicted albuminuria in pediatric patients with T1DM.
本研究旨在确定尿纤溶酶原(一种反映肾小球滤过屏障损伤的丝氨酸蛋白酶)在1型糖尿病(T1DM)儿科患者糖尿病肾病早期检测中的作用。纳入了随访T1DM至少2年的儿科患者以及健康匹配对照。研究了尿纤溶酶原(uPlasminogen)水平和尿纤溶酶原与肌酐比值(uPlgCR)与尿白蛋白与肌酐比值(uACR)之间的关联,并确定用于预测微量白蛋白尿的uPlasminogen的临界值。共纳入56例T1DM患者和30例健康匹配对照。两组间估计肾小球滤过率(eGFR)以及收缩压和舒张压无显著差异。蛋白尿组的uPlasminogen水平高于对照组(p = 0.001),正常蛋白尿组和蛋白尿组的uPlgCR高于对照组(分别为p = 0.004,p = 0.002)。uPlasminogen和uPlgCR与uACR之间存在弱正相关(分别为r = 0.38,p = 0.004;r = 0.28,p = 0.03)。通过ROC曲线分析评估uPlasminogen预测蛋白尿的诊断性能,曲线下面积(AUC)为0.69(p = 0.02;95%可信区间[0.521 - 0.861]),临界值为7.1 μg/L时,敏感性为75%,特异性为65.5%。
发现uPlasminogen和uPlgCR与蛋白尿呈正相关。此外,uPlasminogen可用于预测蛋白尿。最重要的是,在糖尿病患者出现蛋白尿之前uPlgCR就已升高。在进一步进行纵向验证之前,uPlgCR可能作为糖尿病肾病的潜在早期标志物或治疗靶点。
• 糖尿病患者尿纤溶酶原与蛋白尿相关。
• 尿纤溶酶原和uPlgCR水平与uACR呈显著正相关。本研究的新发现是在微量白蛋白尿出现之前在尿液中检测到uPlgCR,并且uPlasminogen可预测T1DM儿科患者的蛋白尿。