CKAP4 in Extracellular Vesicle-Derived from Podocyte Serves as a Non-Invasive Diagnostic Biomarker for Diabetic Nephropathy and promotes vascular calcification

 

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CKAP4 in Extracellular Vesicle-Derived from Podocyte Serves as a Non-Invasive Diagnostic Biomarker for Diabetic Nephropathy and promotes vascular calcification

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Hongwei
Liang
Hongwei Liang hwliang@cpu.edu.cn China Pharmaceutical University School of Life Science and Technology Nanjing China *
Heng Zhang zhangheng3018@163.com China Pharmaceutical University School of Life Science and Technology Nanjing China -
Yanggang Yuan ygyuan@njmu.edu.cn The First Affiliated Hospital of Nanjing Medical University Department of Nephrology Nanjing China -
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Diabetic nephropathy (DN) is a leading cause of chronic kidney disease and end-stage renal disease, posing significant diagnostic challenges due to the limitations of current clinical biomarkers. The identification of non-invasive, early-stage biomarkers is essential for improving disease outcomes.

We developed a method to isolate urinary extracellular vesicles (uEVs) using wheat germ agglutinin (WGA)-coupled magnetic beads and employed proteomic profiling to identify potential biomarkers for DN. CKAP4, a cytoskeleton-associated protein, was selected as a candidate biomarker. The expression of CKAP4 in uEVs was quantified using flow cytometry and validated through clinical samples from a multicenter cohort, as well as murine models of DN.

Our proteomic analysis revealed CKAP4 as a significantly enriched protein in uEVs from DN patients. Elevated CKAP4 levels were confirmed in urine samples, correlating with disease progression and severity. ROC curve analysis demonstrated excellent diagnostic performance, distinguishing DN from healthy controls, diabetic patients, and those with non-diabetic renal diseases. Furthermore, CKAP4 was found to be involved in vascular calcification in DN, highlighting its potential role in both diagnosis and pathogenesis.

Our proteomic analysis revealed CKAP4 as a significantly enriched protein in uEVs from DN patients. Elevated CKAP4 levels were confirmed in urine samples, correlating with disease progression and severity. ROC curve analysis demonstrated excellent diagnostic performance, distinguishing DN from healthy controls, diabetic patients, and those with non-diabetic renal diseases. Furthermore, CKAP4 was found to be involved in vascular calcification in DN, highlighting its potential role in both diagnosis and pathogenesis.

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