title: Urinary Extracellular Vesicles: Potential Biomarkers of Renal Function in Diabetic Patients.
abstract: 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, and glycated hemoglobin (HbA1c) below 7% was a threshold for properly controlled diabetic patients (CD) and poorly controlled diabetic patients (UD). Patients were further divided into two groups: diabetic patients without renal failure (NRF) and with renal failure (RF) 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 offline with mass spectrometry (MALDI-TOF-MS/MS) was applied for proteomic analysis. RF had reduced density of EVs compared to NRF. The size distribution study showed that CD had larger EVs (mode) than UD (115 versus 109 nm;p< 0.05); nevertheless the mean EVs diameter was smaller in controls than in the CD group (123 versus 134 nm;p< 0.05). It was demonstrated that EVs are abundant in urine. Albumin, uromodulin, and number of unique proteins related to 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.
authors.affiliation: Department of Medical Physics, Marian Smoluchowski Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, 30-348 Kraków, Poland.
authors.forename: Agnieszka
authors.identifier: 0000-0003-0278-725X
authors.initials: A
authors.lastname: Kamińska
authors.affiliation: Department of Chemistry, Loughborough University, Loughborough LE11 3TU, UK.
authors.forename: Mark
authors.initials: M
authors.lastname: Platt
authors.affiliation: Laboratory of High Resolution Mass Spectrometry, Regional Laboratory of Physicochemical Analysis and Structural Research, Faculty of Chemistry, Jagiellonian University, 30-060 Kraków, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Kasprzyk
authors.affiliation: Department of Diagnostics, Chair of Clinical Biochemistry, Jagiellonian University Medical College, 31-501 Kraków, Poland.
authors.forename: Beata
authors.initials: B
authors.lastname: Kuśnierz-Cabala
authors.affiliation: St' Queen Jadwiga Clinical District Hospital No. 2, 35-301 Rzeszów, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gala-Błądzińska
authors.affiliation: Department of Cell Biology and Imaging, Institute of Zoology, Faculty of Biology and Earth Sciences, Jagiellonian University, 30-387 Kraków, Poland.
authors.forename: Olga
authors.initials: O
authors.lastname: Woźnicka
authors.affiliation: Department of Solid State Physics, Marian Smoluchowski Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, 30-348 Kraków, Poland.
authors.forename: Benedykt R
authors.initials: BR
authors.lastname: Jany
authors.affiliation: Department of Solid State Physics, Marian Smoluchowski Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, 30-348 Kraków, Poland.
authors.forename: Franciszek
authors.initials: F
authors.lastname: Krok
authors.affiliation: Laboratory of High Resolution Mass Spectrometry, Regional Laboratory of Physicochemical Analysis and Structural Research, Faculty of Chemistry, Jagiellonian University, 30-060 Kraków, Poland; Department of Analytical Chemistry, Faculty of Chemistry, Jagiellonian University, 30-060 Kraków, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Piekoszewski
authors.affiliation: Department of Nephrology, Jagiellonian University Medical College, 31-501 Kraków, Poland.
authors.forename: Marek
authors.initials: M
authors.lastname: Kuźniewski
authors.affiliation: Department of Medical Physics, Marian Smoluchowski Institute of Physics, Faculty of Physics, Astronomy and Applied Computer Science, Jagiellonian University, 30-348 Kraków, Poland.
authors.forename: Ewa Ł
authors.identifier: 0000-0003-3589-1715
authors.initials: EŁ
authors.lastname: Stępień
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology* / Q000652:urine; D003928:Diabetic Nephropathies / Q000175:diagnosis* / Q000503:physiopathology / Q000652:urine; D000067128:Extracellular Vesicles; D005260:Female; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers