Changes in plasmatic miR-126-3p, miR 217, and miR 504, reduced microparticle size, and increased total oxidative status/total antioxidant capacity in diabetes kidney disease

Diabetic kidney disease (DKD) is an important cause of morbimortality in the adult population with Type 1 Diabetes Mellitus (T1DM). Our cross-sectional study explored the association of abnormalities in extracellular vehicles (EVs), microRNAs, and oxidative stress markers in three distinct groups of clinical outpatients: normal controls, T1DM (without DKD), and DKD. Clinical and biochemical data were obtained from these groups. The isolation and characterization of EVs from serum were obtained through a series of processes, including the ultracentrifugation and characterization of EVs was identified by specific protein markers by western blot morphology checked by Scanning Electron Microscopy. EVs particle size and concentration were determined by NanoSight NS300 instrument (Malvern Panalytical, UK). Total Oxidant Status (TOS), Total Antioxidant Capacity (TAC), Advanced Oxidation of Protein Products (AOPP), (Ferric Reducing Antioxidant Power), C reactive Protein, Uric Acid, Aloxan levels were determined in the serum or the plasma. MicroRNA were accessed by RT-PCR. Overall, 124 patients were evaluated: 61 normal controls, 42 T1DM (without DKD), and 21 DKD defined according the KDIGO guidelines. The three groups were similar regarding age (mean±SD) of 40.3±13.7 years, BMI 25.8±5.1 Kg/m2, and Abdominal Circumference 89.6±12.3 cm. The albumin/creatinine ratio was statistically different among the groups, being its (median [95%CI]) of 4.0 [3.9-5.14] mg/g in Controls, 6.4[5.5-10.0]mg/g in T1DM, and 81.4 [48.5 -1415] mg/g in DKD (p=0.001). The DKD patients exhibited higher SBP and an increased proportion of retinopathy and neuropathy than T1DM, but HBa1c levels were similar between the two diabetes groups. Patients with DKD show an increased TOS/TAC Ratio (μmol H2O2 Equiv/L /mmol Trolox Equiv/L) (ANOVA p=0.001) superior to T1DM and controls. Interestingly, T1DM exhibited an increased TOS/TAC Ratio than Controls. There was a gradual decrease in EVs size (but not concentration) in patients with DKD in comparison to T1DM and controls, and T1DM with controls. The mean of the moda size of EVs was (mean+SE) 144.5±3.04 nm in Controls versus 136.14±3.5 nm in T1DM, and 135.4±3.6nm in DKD (ANOVA p=0.04). MiR-126-3p and miR 217 were respectively decreased and increased in DKD versus controls (ANOVA p=0.002). MiR 504 exhibited a dicotomic pattern, being higher in T1DM without DKD in comparison to DKD group (p=0.02). Overall, our results suggest an association of increased oxidative stress status (TOS/TAC ratio) and reduced microvesicles size in the presence of T1DM; both abnormalities progress towards the development of DKD. The disruption of MicroRNAs related to endothelial factors or inflammation may suggest their role in the pathogenesis of diabetes, but longitudinal studies are necessary to predict the real risk to the development of DKD [1] [2] [3] [4] [5] [6] [7] [8] [9] [10].

Publication History

Article published online:
28 May 2025

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