Vagal stimulation in brain dead donor rats decreases chronic allograft nephropathy in recipients

Although it has been shown that a vagus nerve stimulation of brain dead (BD) donors leads to an improvement of renal function in recipients in an acute allograft rejection model, its influence on chronic allograft nephropathy is still unknown. In the present study, we assessed the influence of donor vagus nerve stimulation on survival, renal function and histology in a chronic allograft model. Brain death was induced in Fisher rats, and electro-stimulation of the vagus nerve was applied in one group (BD + vagus) during the whole course of BD (6 h). Unstimulated BD Fisher donor rats served as controls. Allogeneic Lewis rats were used as recipients and no immunosuppressive medication was administered. Blood and urine samples were collected every second week. Banff classification was assessed from harvested allografts. Vagal stimulation of BD donors resulted in an improved survival of recipients. Long-term renal function was significantly better in these recipients as reflected by improved creatinine clearance. Banff classification revealed significantly reduced vasculopathy and less tubulopathy in the BD + vagus group. In conclusion, our data demonstrate a long-lasting beneficial effect of vagus nerve stimulation in BD donors on the renal transplantation outcome. Hence, activation of the cholinergic anti-inflammatory pathway in BD donors may represent a novel therapeutic modality to reduce chronic allograft nephropathy without any side effects for the recipient.