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

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: 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.