Urinary extracellular vesicles – potential biomarkers of renal function in diabetic patients
Kamińska, A., Platt, M., Kasprzyk, J., Kuśnierz-Cabala, B., Gala-Błądzińska, A., Woźnicka, O., ... & Stępień, E. Ł. Urinary extracellular vesicles–potential biomarkers of renal function in diabetic patients.
The aim of this study was to check the relationship between the density of urinary EVs, their size distribution and the progress of early renal damage in type 2 diabetic patients (DMt2). Patients were enrolled to this study, glycated hemoglobin (HbA1c) below 7% was a threshold for properly (CD) and poorly (UD) controlled diabetes. Patients were further divided into two groups: diabetics without (NRF) and with (RF) renal failure according to the Glomerular Filtration Rate. Density and diameter of EVs were determined by Tunable Resistive Pulse Sensing. Additionally, EVs were visualized by means of Transmission and Environmental Scanning Electron Microscopy. Nano-liquid chromatography coupled off-line with mass spectrometry (MALDI-TOF-MS/MS) was applied for proteomic analysis. RF patients had reduced density of EVs compared to NRF ones. The size distribution study showed that CD patients had larger EVs (mode) than UD patients (115 vs. 109 nm; p<0.05), nevertheless the mean EVs diameter was smaller in controls than in the CD group (123 vs. 134 nm; p<0.05). It was demonstrated that EVs are abundant in urine. Albumin, uromodulin and number of unique proteins related with cell stress and secretion were detected in the EVs fraction. Density and size of urinary EVs reflect deteriorated renal function and can be considered as potential renal damage biomarkers.
Key words: diabetes; extracellular vesicles; proteomics; diabetic nephropathy; tunable resistive pulse sensing; urinary vesicles.