Graduation Year
2017
Document Type
Dissertation
Degree
Ph.D.
Degree Name
Doctor of Philosophy (Ph.D.)
Degree Granting Department
Medical Sciences
Major Professor
Ruisheng Liu, M.D., Ph.D.
Committee Member
Byeong Jake Cha, Ph.D.
Committee Member
Javier Cuevas, Ph.D.
Committee Member
Alfredo M. Peguero-Rivera, M.D.
Committee Member
Daniel Kay-Pong Yip, Ph.D.
Keywords
Acute Kidney Injury, Ischemia Reperfusion Injury, Chronic Kidney Disease, Renal Hemodynamic
Abstract
Ischemia and reperfusion are natural steps during kidney transplantation, and IRI is considered one of the most important nonspecific factors affecting allograft dysfunction. Transplanted organs experience several episodes of ischemia, in which cold ischemia occurs during allograft storage in preservation solutions.
Even though cold ischemia has been studied extensively, all of the studies have been carried out in vitro and ex vivo models. There is no in vivo model available to examine renal IRI induced solely by cold ischemia.
In the present study, we developed an in vivo mouse model to study renal IRI induced exclusively by cold ischemia through clamping the renal pedicle for 1 to 5 hours. During the ischemic phase, blood was flushed from the kidney with cold saline through a small opening on the renal vein. The kidney was kept cold in a kidney cup with circulating cooled saline, while the body temperature was maintained at 37℃ during the experiment. The level of kidney injury was evaluated by plasma creatinine, KIM-1, NAGL, GFR, and histology.
Plasma creatinine was significantly increased from 0.15±0.04 mg/dl in the sham group to 1.14±0.21 and 2.65±0.14 mg/dl in 4 and 5-hours ischemia groups at 24 hours after cold IRI. The plasma creatinine in mice with ischemic time <3 hours demonstrated no significant increase compared with sham mice. Changes in KIM-1, NAGL, GFR and histology were similar to plasma creatinine. 65
In summary, we developed and characterized a novel in vivo IRI-induced AKI mouse model exclusively produced by cold ischemia.
Scholar Commons Citation
Wei, Jin, "Acute Kidney Injury and Chronic Kidney Disease" (2017). USF Tampa Graduate Theses and Dissertations.
https://digitalcommons.usf.edu/etd/6780