CKAP4 in Extracellular Vesicle‐Derived From Podocyte Serves as a Non‐Invasive Diagnostic Biomarker for Diabetic Nephropathy and Promotes Vascular Calcification

Reliable non-invasive biomarkers for early detection of diabetic nephropathy (DN), a leading cause of chronic kidney disease, remain limited. In this study, we isolate urinary extracellular vesicles (uEVs) using wheat germ agglutinin (WGA)-conjugated magnetic beads and identify cytoskeleton-associated protein 4 (CKAP4) as a potential diagnostic biomarker for DN. Proteomic profiling and flow cytometry show that CKAP4 levels are significantly higher in uEVs from DN patients than in those from diabetic, non-diabetic renal disease (NDRD) and healthy control groups. Receiver operating characteristic (ROC) analysis demonstrates excellent diagnostic performance, with area under the curve (AUC) values of 0.9998 (sensitivity = 98.77%, specificity = 100%) for DN versus controls, and 0.9859 (sensitivity = 95.72%, specificity = 99.24%) for DN versus diabetes mellitus. CKAP4 levels, elevated even at early-stage DN, positively correlate with glomerulosclerosis, increasing with the severity of interstitial fibrosis and tubular atrophy (IFTA). Mechanistically, CKAP4-containing EVs derived from high glucose-treated podocytes promote vascular calcification in vascular smooth muscle cells via YAP signalling. These findings identify CKAP4 in podocyte-derived uEVs as a robust non-invasive biomarker for early DN detection and provide new insights into the vascular pathology associated with the disease.

Authors

Institutions

Publication Details

Journal
Journal of Extracellular Vesicles
Published
2025-11-29
DOI
https://doi.org/10.1002/jev2.70208
Primary Topic
Extracellular vesicles in disease
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

CKAP4 in Extracellular Vesicle‐Derived From Podocyte Serves as a Non‐Invasive Diagnostic Biomarker for Diabetic Nephropathy and Promotes Vascular Calcification

Yangtian Wang, Dafa Ding, Shuang Qu, Heng Zhang et al.
Journal of Extracellular Vesicles
Extracellular vesicles in disease
article

CKAP4 in Extracellular Vesicle‐Derived From Podocyte Serves as a Non‐Invasive Diagnostic Biomarker for Diabetic Nephropathy and Promotes Vascular Calcification

Yangtian Wang, Dafa Ding, Shuang Qu, Heng Zhang, Laping Chu, Zen Ke, Chong Wu, Jia Meng, Min Zhang, Yang Bai, Fang Lu, Yanggang Yuan, Meng Liu, Jie Li, Qian Li, Lizhi Lv, Liang Hong-wei, Gang He, Wu JunXiang, Kaibin Lou
article en

Abstract

Reliable non-invasive biomarkers for early detection of diabetic nephropathy (DN), a leading cause of chronic kidney disease, remain limited. In this study, we isolate urinary extracellular vesicles (uEVs) using wheat germ agglutinin (WGA)-conjugated magnetic beads and identify cytoskeleton-associated protein 4 (CKAP4) as a potential diagnostic biomarker for DN. Proteomic profiling and flow cytometry show that CKAP4 levels are significantly higher in uEVs from DN patients than in those from diabetic, non-diabetic renal disease (NDRD) and healthy control groups. Receiver operating characteristic (ROC) analysis demonstrates excellent diagnostic performance, with area under the curve (AUC) values of 0.9998 (sensitivity = 98.77%, specificity = 100%) for DN versus controls, and 0.9859 (sensitivity = 95.72%, specificity = 99.24%) for DN versus diabetes mellitus. CKAP4 levels, elevated even at early-stage DN, positively correlate with glomerulosclerosis, increasing with the severity of interstitial fibrosis and tubular atrophy (IFTA). Mechanistically, CKAP4-containing EVs derived from high glucose-treated podocytes promote vascular calcification in vascular smooth muscle cells via YAP signalling. These findings identify CKAP4 in podocyte-derived uEVs as a robust non-invasive biomarker for early DN detection and provide new insights into the vascular pathology associated with the disease.

Journal of Extracellular VesiclesVol. 14(12)
Jiangnan University (CN), China Pharmaceutical University (CN), Nanjing Drum Tower Hospital (CN), Wuxi Fourth People's Hospital (CN), Kangmei Pharmaceutical (China) (CN), Second Affiliated Hospital of Nanjing Medical University (CN), Jiangsu Province Hospital (CN), Nanjing Medical University (CN)
Jiangsu Commission of Health, National Natural Science Foundation of China
Openalex Percentile: Top 66%
Extracellular vesicles in disease
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.