This study evaluated the effects of bone marrow-derived mesenchymal stem cells (BMSCs) or their conditioned medium (CM) on the repair and prevention of Acute Kidney Injury (AKI) induced by gentamicin (G). Animals received daily injections of G up to 20 days. On the 10th day, injections of BMSCs, CM, CM+trypsin, CM+RNase or exosome-like microvesicles extracted from the CM were administered. In the prevention groups, the animals received the BMSCs 24 h before or on the 5th day of G treatment. Creatinine (Cr), urea (U), FENa and cytokines were quantified. The kidneys were evaluated using hematoxylin/eosin staining and immunohystochemistry. The levels of Cr, U and FENa increased during all the periods of G treatment. The BMSC transplantation, its CM or exosome injections inhibited the increase in Cr, U, FENa, necrosis, apoptosis and also increased cell proliferation. The pro-inflammatory cytokines decreased while the anti-inflammatory cytokines increased compared to G. When the CM or its exosomes were incubated with RNase (but not trypsin), these effects were blunted. The Y chromosome was not observed in the 24-h prevention group, but it persisted in the kidney for all of the periods analyzed, suggesting that the injury is necessary for the docking and maintenance of BMSCs in the kidney. In conclusion, the BMSCs and CM minimized the G-induced renal damage through paracrine effects, most likely through the RNA carried by the exosome-like microvesicles. The use of the CM from BMSCs can be a potential therapeutic tool for this type of nephrotoxicity, allowing for the avoidance of cell transplantations.

We measured plasma‐derived extracellular vesicle (EV) proteins and their microRNA (miRNA) cargos in normoglycemic (NG), glucose intolerant (GI), and newly diagnosed diabetes mellitus (DM) in middle‐aged male participants of the Brazilian Longitudinal Study of Adult Health (ELSA‐Brazil). Mass spectrometry revealed decreased IGHG‐1 and increased ITIH2 protein levels in the GI group compared with that in the NG group and higher serotransferrin in EVs in the DM group than in those in the NG and GI groups. The GI group also showed increased serum ferritin levels, as evaluated by biochemical analysis, compared with those in both groups. Seventeen miRNAs were differentially expressed (DEMiRs) in the plasma EVs of the three groups. DM patients showed upregulation of miR‐141‐3p and downregulation of miR‐324‐5p and ‐376c‐3p compared with the NG and GI groups. The DM and GI groups showed increased miR‐26b‐5p expression compared with that in the NG group. The DM group showed decreased miR‐374b‐5p levels compared with those in the GI group and higher concentrations than those in the NG group. Thus, three EV proteins and five DEMiR cargos have potential prognostic importance for diabetic complications mainly associated with the immune function and iron status of GI and DM patients.

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Several studies have demonstrated an important association between altered lipid metabolism and the development of kidney injury because of a high-fat diet. Fructose is also closely associated with renal injury. We opted for a combination of fructose and saturated fats in a diet (DH) that is a model known to induce renal damage in order to evaluate whether soy isoflavones could have promising use in the treatment of renal alterations. After two months of ingestion, there was an expansion of visceral fat, which was associated with long-term metabolic disorders, such as sustained hyperglycemia, insulin resistance, polyuria, dyslipidemia, and hypertension. Additionally, we found a decrease in renal blood flow and an increase in renal vascular resistance. Biochemical markers of chronic kidney disease were detected; there was an infiltration of inflammatory cells with an elevated expression of proinflammatory cytokines (tumor necrosis factor-α, interleukin (IL)-6, and IL-1β), the activation of the renin–angiotensin system, and oxidative/nitrosative stress. Notably, in rats exposed to the DH diet for 120 days, the concomitant treatment with isoflavones after 60 days was able to revert metabolic parameters, renal alterations, and oxidative/nitrosative stress. The beneficial effects of isoflavones in the kidney of the obese rats were found to be mediated by expression of peroxisome proliferator-activated receptor gamma (PPAR-γ).