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.

Available for download on Wednesday, May 09, 2018

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