Abstract 433: Renal Effects of Everolimus Versus Bone Marrow-derived Stem Cells in Rat Model of Glomerulonephritis

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The progression of renal disease is mainly influenced by degree of glomerular endothelial injury and effectiveness of glomerular endothelial repair. Considerable research efforts have recently been undertaken to examine glomerular endothelial repair by progenitor cells. We hypothesize that bone marrow-derived stem cells (BMDSCs) ameliorate experimental glomerulonephritis by restoring glomerular endothelial barrier function through improving the repair process. Anti-Thy1-glomerulonephritis was induced in Sprague Dawley rats by a single injection of an antibody against Thy1, which is mainly expressed on glomerular mesangial cells. Rats were then treated with the immunosuppressant everolimus (EV) daily or injected with isolated BMDSCs after one week of injection of anti-Thy1. After nine days of Injection of anti-Thy1, glomerular albumin permeability and albuminuria were significantly increased when compared to control group (P< 0.05). EV was superior than BMDSCs in attenuating the increase in glomerular albumin permeability and albuminuria in anti-Thy1 injected rats. However, only EV treatment significantly reduced the markers of glomerular injury, nephrinuria and podocalyxin excretion levels in anti-Thy1 injected rats (nephrinuria was 0.4± 0.1 vs. 0.8± 0.02 mg/day and podocalyxin excretion was 7± 1 vs. 11± 1 μg/day in EV treated vs. untreated anti-Thy1 injected rats, P< 0.05). Anti-Thy1 injected rats also showed hypercellular glomeruli with loss of Bowman space and variable number of lymphocyte and EV treatment partially restored these pathophysiological changes whereas BMDSCs had no significant effect. EV treatment also reduced number of renal CD3+ and macrophage and lowered IL-17 and caspase 3 levels in the anti-Thy1 injected rat kidneys. These data suggest that EV early treatment preserve glomerular endothelial barrier function in Anti-Thy1-induced glomerulonephritis via anti-apoptotic and anti-inflammatory mechanisms.

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