Plasma levels of the lymphangiogenic factors VEGF-C, VEGF-D, and CXCL-12 are elevated in advanced diabetic nephropathy

Objective Early biomarkers for diabetic nephropathy progression remain limited. This study aims to investigate whether plasma levels of VEGF-C, VEGF-D, and CXCL-12 can reflect the severity of diabetic kidney disease (DKD), and to evaluate their potential as biomarkers for disease monitoring.Methods...

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Main Authors: Qingshan Tian, Fan Zhang, Zhichao Yang, Ji Miao, Hao Wu, Zhenzhong Zheng
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Renal Failure
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Online Access:https://www.tandfonline.com/doi/10.1080/0886022X.2025.2536196
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author Qingshan Tian
Fan Zhang
Zhichao Yang
Ji Miao
Hao Wu
Zhenzhong Zheng
author_facet Qingshan Tian
Fan Zhang
Zhichao Yang
Ji Miao
Hao Wu
Zhenzhong Zheng
author_sort Qingshan Tian
collection DOAJ
description Objective Early biomarkers for diabetic nephropathy progression remain limited. This study aims to investigate whether plasma levels of VEGF-C, VEGF-D, and CXCL-12 can reflect the severity of diabetic kidney disease (DKD), and to evaluate their potential as biomarkers for disease monitoring.Methods Patients were divided into normal albuminuria group (UmAlb < 30 mg/24 h, n = 30), microalbuminuria group (UmAlb 30–300 mg/24 h, n = 30) and macroalbuminuria group (UmAlb >300 mg/24 h, n = 30). Healthy individuals were included as control group (n = 30). Plasma levels of vascular endothelial growth factor-C (VEGF-C), vascular endothelial growth factor-D (VEGF-D), and chemokine ligand 12 (CXCL-12) were measured.Results The plasma levels of VEGF-C, VEGF-D, and CXCL-12 were significantly increased in all type 2 diabetic kidney disease groups. Correlation analysis revealed that plasma VEGF-C, VEGF-D and CXCL-12 levels were positively correlated with plasma creatinine and urinary microalbumin. Furthermore, these levels were inversely correlated with estimated glomerular filtration rate. In order to distinguish DKD patients in the normal albuminuria group, microalbuminuria group, and macroalbuminuria group, the areas under the receiver operating characteristic curve (AUC-ROCs) of VEGF-C was 0.668 (95%CI: 0.531–0.805), 0.790 (95%CI: 0.678–0.901), and 0.850 (95%CI: 0.756–0.944), respectively. For VEGF-D, the AUC-ROCs were 0.718 (95%CI: 0.587–0.848), 0.873 (95%CI: 0.783–0.963), and 0.931 (95%CI: 0.872–0.991), respectively. Finally, for CXCL-12, the AUC-ROCs were 0.687 (95%CI: 0.554–0.820), 0.816 (95%CI: 0.710–0.921), and 0.903 (95%CI: 0.829–0.977), respectively.Conclusion Plasma VEGF-C, VEGF-D, and CXCL-12 levels is of great value for early diagnosis and assessment of diabetic kidney disease severity. This suggests that these may serve as valuable surrogate markers for clinical outcomes in DKD.
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spelling doaj-art-1ffd03afd2f441e9bb9612bd7975198c2025-08-20T03:45:11ZengTaylor & Francis GroupRenal Failure0886-022X1525-60492025-12-0147110.1080/0886022X.2025.2536196Plasma levels of the lymphangiogenic factors VEGF-C, VEGF-D, and CXCL-12 are elevated in advanced diabetic nephropathyQingshan Tian0Fan Zhang1Zhichao Yang2Ji Miao3Hao Wu4Zhenzhong Zheng5Department of Cardiology, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDepartment of Nephrology, Haidian Hospital (Haidian section of Peking University Third Hospital), Beijing, ChinaDepartment of Cardiology, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaDivision of Endocinology, Boston Children’s Hospital, Harvard Medical School, Boston, MA, USAVascular Biology Program, Boston Children’s Hospital, Department of Surgery, Harvard Medical School, Boston, MA, USADepartment of Cardiology, The 1st Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, ChinaObjective Early biomarkers for diabetic nephropathy progression remain limited. This study aims to investigate whether plasma levels of VEGF-C, VEGF-D, and CXCL-12 can reflect the severity of diabetic kidney disease (DKD), and to evaluate their potential as biomarkers for disease monitoring.Methods Patients were divided into normal albuminuria group (UmAlb < 30 mg/24 h, n = 30), microalbuminuria group (UmAlb 30–300 mg/24 h, n = 30) and macroalbuminuria group (UmAlb >300 mg/24 h, n = 30). Healthy individuals were included as control group (n = 30). Plasma levels of vascular endothelial growth factor-C (VEGF-C), vascular endothelial growth factor-D (VEGF-D), and chemokine ligand 12 (CXCL-12) were measured.Results The plasma levels of VEGF-C, VEGF-D, and CXCL-12 were significantly increased in all type 2 diabetic kidney disease groups. Correlation analysis revealed that plasma VEGF-C, VEGF-D and CXCL-12 levels were positively correlated with plasma creatinine and urinary microalbumin. Furthermore, these levels were inversely correlated with estimated glomerular filtration rate. In order to distinguish DKD patients in the normal albuminuria group, microalbuminuria group, and macroalbuminuria group, the areas under the receiver operating characteristic curve (AUC-ROCs) of VEGF-C was 0.668 (95%CI: 0.531–0.805), 0.790 (95%CI: 0.678–0.901), and 0.850 (95%CI: 0.756–0.944), respectively. For VEGF-D, the AUC-ROCs were 0.718 (95%CI: 0.587–0.848), 0.873 (95%CI: 0.783–0.963), and 0.931 (95%CI: 0.872–0.991), respectively. Finally, for CXCL-12, the AUC-ROCs were 0.687 (95%CI: 0.554–0.820), 0.816 (95%CI: 0.710–0.921), and 0.903 (95%CI: 0.829–0.977), respectively.Conclusion Plasma VEGF-C, VEGF-D, and CXCL-12 levels is of great value for early diagnosis and assessment of diabetic kidney disease severity. This suggests that these may serve as valuable surrogate markers for clinical outcomes in DKD.https://www.tandfonline.com/doi/10.1080/0886022X.2025.2536196Type 2 diabetic kidney diseaseVEGF-cVEGF-dCXCL-12
spellingShingle Qingshan Tian
Fan Zhang
Zhichao Yang
Ji Miao
Hao Wu
Zhenzhong Zheng
Plasma levels of the lymphangiogenic factors VEGF-C, VEGF-D, and CXCL-12 are elevated in advanced diabetic nephropathy
Renal Failure
Type 2 diabetic kidney disease
VEGF-c
VEGF-d
CXCL-12
title Plasma levels of the lymphangiogenic factors VEGF-C, VEGF-D, and CXCL-12 are elevated in advanced diabetic nephropathy
title_full Plasma levels of the lymphangiogenic factors VEGF-C, VEGF-D, and CXCL-12 are elevated in advanced diabetic nephropathy
title_fullStr Plasma levels of the lymphangiogenic factors VEGF-C, VEGF-D, and CXCL-12 are elevated in advanced diabetic nephropathy
title_full_unstemmed Plasma levels of the lymphangiogenic factors VEGF-C, VEGF-D, and CXCL-12 are elevated in advanced diabetic nephropathy
title_short Plasma levels of the lymphangiogenic factors VEGF-C, VEGF-D, and CXCL-12 are elevated in advanced diabetic nephropathy
title_sort plasma levels of the lymphangiogenic factors vegf c vegf d and cxcl 12 are elevated in advanced diabetic nephropathy
topic Type 2 diabetic kidney disease
VEGF-c
VEGF-d
CXCL-12
url https://www.tandfonline.com/doi/10.1080/0886022X.2025.2536196
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