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.
Highlights
The incidence of diabetes mellitus has grown significantly throughout the world and diabetes becomes the most common cause of kidney injury
We observed a negative tendency between extracellular vesicles (EVs) density and serum glucose level in Uncontrolled diabetes (UD) (R = −0.33) and negative correlation in renal failure (RF) (R = −0.66) patients (Figure 2)
The age related negative relationship was observed in controlled diabetic patients (CD) and Diabetic patients without renal failure PBS (NRF) group in terms of creatinine clearance (GFR)
Summary
The incidence of diabetes mellitus has grown significantly throughout the world and diabetes becomes the most common cause of kidney injury. 30 percent of patients with diabetes of type 1 (DMt1) and 10 to 40 percent of those with type 2 (DMt2) will suffer from renal damage [1,2,3]. Most of cells release small membrane spherical structures called extracellular vesicles (EVs) which can be classified into three groups: exosomes (50–100 nm), Journal of Diabetes Research microvesicles (100–1000 nm), and apoptotic bodies. These vesicles differ in their composition and subcellular origin. Urine is a rich reservoir of these vesicles which originate from the cells facing the urinary lumen (epithelial cells). The urinary EVs can reflect the state of the damage of the kidney. Changes in excretion rates of specific proteins can have predictive value in the early diagnosis of renal damage [10]
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