Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Exhibit Hall E
The overall goal of this study is to further evaluate the effectiveness of a potential new therapy designed to minimize damage during cold preservation, increase the donor pool, and improve renal transplant outcomes. Our published reports showed that cold storage induces mitochondrial and renal damage, and we recently reported that a mitochondrial targeted antioxidant, MitoQ, blunted mitochondrial damage in a porcine kidney model. New studies are needed in an animal model of cold storage plus transplantation as well as pilot studies using discarded human kidneys treated with MitoQ.
Methods: Male rat kidneys were isolated and cold stored in UW solution for 4 hr +/- MitoQ (100 μM) followed by transplantation. Likewise, discarded human kidneys (pairs) were cold stored +/- MitoQ (100 μM) followed by ex vivo reperfusion to simulate human kidney transplantation. Renal function was determined via measurement of serum creatinine and/or creatinine clearance. Cell death and reactive oxygen species (ROS) were also assessed using immunohistochemistry. Renal mitochondrial function was assessed via high resolution respirometry (oxygen consumption) of renal biopsies, ATP measurement, and blue native gel electrophoresis.
Results: Renal cold storage plus transplantation lead to decreased respiratory complex I and II/III function, reduced ATP, increased cell death, and renal damage. MitoQ addition during cold storage increased ATP levels, decreased cell death and ROS, and improved renal function following cold storage plus transplantation. Early results using discarded human kidneys also suggest a protective role for MitoQ in these damaged donor kidneys.
Summary: These studies suggest cold storage plus transplantation induces mitochondrial and renal damage and excitingly that inclusion of MitoQ during cold storage leads to protection. Further studies are underway to determine the molecular targets leading to mitochondrial damage as well as protection following MitoQ treatment.
Supported by NIH DK089659 and UAMS TRI UL1TR000039 (LAMC).
To cite this abstract in AMA style:MacMillan-Crow L, Parajuli N, Borja-Cacho D. Can MitoQ Improve Renal and Mitochondrial Function Following Cold Storage and Transplantation? [abstract]. Am J Transplant. 2015; 15 (suppl 3). https://atcmeetingabstracts.com/abstract/can-mitoq-improve-renal-and-mitochondrial-function-following-cold-storage-and-transplantation/. Accessed June 6, 2020.
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