ToF-SIMS metabolomic analysis of urinary extracellular vesicles to identify potential markers for diabetic kidney disease in type 1 diabetes

IF 2.5 4区医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in medical sciences Pub Date : 2026-03-01 Epub Date: 2026-04-01 DOI:10.1016/j.advms.2026.03.008

Magdalena E. Skalska , Agnieszka Kamińska , Paulina Suduł , Jakub Kurdziel , Tomasz Klupa , Maciej Małecki , Ewa Ł. Stępień

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引用次数: 0

Abstract

Purpose

Kidney damage is a significant concern in type 1 (T1DM) and type 2 (T2DM) diabetes mellitus, with diagnoses of chronic kidney disease (CKD) based on glomerular filtration rate and albumin excretion. An early marker for kidney damage is needed, and extracellular vesicles (EVs) show promise in this area. These nanostructures facilitate the transport of proteins, lipids, and nucleic acids between cells and undergo structural changes that can indicate the presence of disease.

Materials and methods

Our study employed time-of-flight secondary ion mass spectrometry (ToF-SIMS) to analyse lipid content in urinary EVs (uEVs) from 29 individuals with well-controlled T1DM (15 years duration, HbA1c ∼7%) and 16 healthy controls. uEVs were analysed using tunable resistive pulse sensing (TRPS) to determine size, concentration, and zeta potential, and by ToF-SIMS in both positive and negative ion modes to profile lipid- and amino acid-related ions.

Results

T1DM uEVs exhibited a more negative zeta potential (−27.65 ± 1.51 mV vs −18.43 ± 0.87 mV) and higher particle concentration ((7.1 ± 0.7) × 10¹¹ vs (6.4 ± 0.9) × 10¹⁰ particles/mL), while mean particle diameters were similar between groups. TOF-SIMS showed broadly comparable class-level proportions of lipids and amino acids; however, several individual lipid ions, including diacylglycerols, sphingolipids and selected fatty acids, displayed measurable differences. Amino-acid-related ions showed minor variations without major shifts in overall composition.

Conclusions

These findings suggest that uEVs may reflect pathological processes in individuals with T1DM without CKD. However, further research is necessary to confirm whether uEVs can be markers for CKD.

Abstract Image

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尿细胞外囊泡的ToF-SIMS代谢组学分析鉴定1型糖尿病患者糖尿病肾病的潜在标志物

目的：肾脏损害是1型（T1DM）和2型（T2DM）糖尿病患者的一个重要问题，慢性肾脏疾病（CKD）的诊断基于肾小球滤过率和白蛋白排泄。需要一种肾脏损伤的早期标志物，细胞外囊泡（EVs）在这一领域显示出希望。这些纳米结构促进蛋白质、脂质和核酸在细胞之间的运输，并发生结构变化，表明疾病的存在。材料和方法：我们的研究采用飞行时间二次离子质谱法（ToF-SIMS）分析了29名控制良好的T1DM患者（病程15年，HbA1c ~ 7%）和16名健康对照者尿液EVs （uEVs）中的脂质含量。使用可调电阻脉冲传感（TRPS）来确定uev的大小、浓度和zeta电位，并通过ToF-SIMS在正离子和负离子模式下分析脂质和氨基酸相关离子。结果：T1DM uev具有更高的zeta电位（-27.65±1.51 mV vs -18.43±0.87 mV）和更高的颗粒浓度（（7.1±0.7）× 1011 vs（6.4±0.9）× 1010颗粒/mL），而两组平均颗粒直径相似。TOF-SIMS显示脂质和氨基酸的类水平比例大致相当；然而，几种单独的脂质离子，包括二酰基甘油、鞘脂和选定的脂肪酸，显示出可测量的差异。氨基酸相关离子表现出较小的变化，但总体组成没有大的变化。结论：这些发现提示uEVs可能反映了无CKD的T1DM患者的病理过程。然而，uEVs是否可以作为CKD的标志物，还需要进一步的研究来证实。

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来源期刊

Advances in medical sciences 医学-医学：研究与实验

CiteScore

5.00

自引率

0.00%

发文量

审稿时长

25 days

期刊介绍： Advances in Medical Sciences is an international, peer-reviewed journal that welcomes original research articles and reviews on current advances in life sciences, preclinical and clinical medicine, and related disciplines. The Journal’s primary aim is to make every effort to contribute to progress in medical sciences. The strive is to bridge laboratory and clinical settings with cutting edge research findings and new developments. Advances in Medical Sciences publishes articles which bring novel insights into diagnostic and molecular imaging, offering essential prior knowledge for diagnosis and treatment indispensable in all areas of medical sciences. It also publishes articles on pathological sciences giving foundation knowledge on the overall study of human diseases. Through its publications Advances in Medical Sciences also stresses the importance of pharmaceutical sciences as a rapidly and ever expanding area of research on drug design, development, action and evaluation contributing significantly to a variety of scientific disciplines. The journal welcomes submissions from the following disciplines: General and internal medicine, Cancer research, Genetics, Endocrinology, Gastroenterology, Cardiology and Cardiovascular Medicine, Immunology and Allergy, Pathology and Forensic Medicine, Cell and molecular Biology, Haematology, Biochemistry, Clinical and Experimental Pathology.