Mitochondrial Transplantation By Intraarterial Injection Ameliorates Acute Kidney Injury

Introduction: Acute kidney injury (AKI) is a common clinical disorder and one of the major causes of morbidity and mortality during the postoperative period. In this study, we investigated the safety and efficacy of autologous mitochondrial transplantation by intra-arterial injection for renal protection in a swine model of bilateral renal ischemia-reperfusion injury (IRI). Methods: Female Yorkshire pigs (n=12) underwent percutaneous bilateral temporary occlusion of the renal arteries with balloon-catheters. Following 60 minutes of ischemia, the balloon catheters were deflated and animals received either autologous mitochondria suspended in vehicle (n=6) or vehicle alone (n=6), delivered as a single bolus to the renal arteries. Results: Injected mitochondria were rapidly taken up by the kidney and were distributed throughout the tubular epithelium of the cortex and the medulla. Evaluation of plasma electrolytes, acid-base status, complete blood count and biochemical analysis did not reveal evidence of any adverse effects associated with mitochondrial transplantation. After 24 hours of reperfusion, eGFR and urine output were significantly increased (p<0.01) while plasma creatinine and BUN were significantly decreased (p<0.01) in pigs receiving mitochondria compared to vehicle (Figure 1). Gross anatomy, histopathological analysis, acute tubular necrosis scoring and transmission electron microscopy showed that the renal cortex of vehicle group had extensive coagulative necrosis of primarily proximal tubules, while mitochondrial transplanted kidneys showed only patchy mild acute tubular injury. Renal cortex IL-6 expression had a 3.5-fold significant increase (p<0.05) in vehicle kidneys compared to kidneys receiving mitochondrial transplantation. Conclusions: Mitochondrial transplantation by intra-arterial injection provides renal protection from IRI, significantly enhancing renal function and ameliorating AKI.