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. 2025 Jun 27;184(7):451.
doi: 10.1007/s00431-025-06278-3.

Urinary plasminogen as an early marker of diabetic kidney disease in children with type 1 diabetes mellitus: a cross-sectional study

Mihriban İnözü  1   2 , Gönül Büyükyılmaz  3 , Begüm Avcı  4 , İsmail Selçuk Aygar  5 , Fatma Semsa Çaycı  6   7 , Seyit Ahmet Uçaktürk  8 , Eda Mengen  9 , Sare Gülfem Özlü  6   10 , Umut Selda Bayrakçı  6   10
Affiliations

Urinary plasminogen as an early marker of diabetic kidney disease in children with type 1 diabetes mellitus: a cross-sectional study

Mihriban İnözü et al. Eur J Pediatr. .

Abstract

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.

Conclusion: 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.

What is known: • Urinary plasminogen correlates with albuminuria in diabetic patients.

What is new: • 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.

Keywords: Children; Diabetic kidney disease; Diabetic nephropathy; Plasminogen; Plasminuria; Type 1 diabetes mellitus.

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Conflict of interest statement

Declarations. Ethics approval: The study protocol was approved by the Ethics Committee of our hospital (date 25 March 2019/approval no: 042). The study involving human participants was performed in accordance with the Declaration of Helsinki, and the study protocol was approved by the Medical Research Ethics Committee of Ankara Child Health Hematology-Oncology Training and Research Hospital (Protocol Number: 2019–042). Consent to participate: Informed consent was obtained from all individual participants and their parents included in the study. Competing interest: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
uACR, uPlasminogen, and uPlgCR levels by groups. Abbreviations: uACR (mg/g), urinary albumin/creatinine ratio; uPlasminogen (µg/L), urinary plasminogen; uPlgCR (µg/g), urinary plasminogen/creatinine ratio
Fig. 2
Fig. 2
ROC curve of uPlasminogen in the prediction of albuminuria. Abbreviations: AUC, area under the curve
See this image and copyright information in PMC

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