Kidney Week

Abstract: TH-PO025

Mitochondrial Transplantation by Intra-Arterial Injection Prevents Renal Ischemia-Reperfusion Injury

Session Information

• AKI: Mechanisms - Primary Injury and Repair - I
  November 07, 2019 | Location: Exhibit Hall, Walter E. Washington Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Guariento, Alvise, Harvard Medical School, Boston Children's Hospital, Marblehead, Massachusetts, United States

Alvise Guariento,

• Doulamis, Ilias P., Harvard Medical School, Boston Children's Hospital, Marblehead, Massachusetts, United States

Ilias P. Doulamis,

• Parikh, Samir M., BIDMC/Harvard Medical School, Boston, Massachusetts, United States

Samir M. Parikh,

• Del nido, Pedro J., Harvard Medical School, Boston Children's Hospital, Marblehead, Massachusetts, United States

Pedro J. Del nido,

• Bajwa, Amandeep, University of Tennessee, Memphis, Tennessee, United States

Amandeep Bajwa,

• McCully, James Donald, Harvard Medical School, Boston Children's Hospital, Marblehead, Massachusetts, United States

James Donald McCully,

Background

Mitochondrial transplantation (MT) is a novel clinically validated strategy for the amelioration of organs subjected to ischemia-reperfusion injury (IRI). In this study we investigated the safety of autologous MT and the therapeutic use for renal protection in a swine model of bilateral IRI.

Methods

Yorkshire pigs (n=24; female, 40-50 kg) underwent selective catheterization of the renal arteries under fluoroscopy (Fig. 1 A). Mitochondria (1 x 10⁹ in 10 ml buffer) were delivered as a single bolus (n=6) or serially (3 injections over 60 minutes, n=6) in each of the renal arteries of healthy animals. Another group of animals underwent bilateral temporary occlusion with balloon-catheters (60 minutes of ischemia) followed by 24 hours of reperfusion. Mitochondria (n=6) or Vehicle (n=6) were delivered as a single bolus in each of the renal arteries at the time of reperfusion. Uptake was confirmed by PET-CT images after intra-arterial injection of ¹⁸F-Rhodamine-labeled mitochondria (Fig. 1 B).

Results

MT temporarily increased renal function in the healthy kidney. Intra-arterial injection of mitochondria had no side effects on hemodynamics, systemic inflammatory response and organ function. After 24 hours of reperfusion, MT significantly improved renal function in terms of renal output (p=0.02), serum creatinine (p<0.01), estimated glomerular filtration rate (p=0.03) and blood urea nitrogen (p<0.01) compared to vehicle treated animals (Fig. 1 C-D).

Conclusion

Mitochondrial transplantation by intra-arterial injection is safe and prevents renal IRI.

(A) Experimental Model. (B) Representative PET images 10 minutes post intra-arterial injection of ¹⁸F-Rhodamine-labeled mitochondria. (C-D) Renal function during the entire experiment (C) Creatinine (mg/dL), (D) Blood Urea Nitrogen (mg/dL).

Funding

• Other NIH Support