A Standardized Warm Ischemia Time for the Induction of Injury in Murine Kidney Transplants

One of the cornerstone research models used in our laboratories is the induction of ischemic injury through cold ischemia followed by warm ischemia to donor kidneys to mimic the clinical realities of transplantation. The experimental design of the present study included bilateral nephrectomies on th...

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Bibliographic Details
Published in:Transplantation proceedings 2021-01, Vol.53 (1), p.481-485
Main Authors: Plenter, Robert J., Jain, Swati, Nydam, Trevor L., Jani, Alkesh H.
Format: Article
Language:English
Subjects:
Animals
Cold Ischemia
Creatinine - blood
Disease Models, Animal
Ischemia - physiopathology
Kidney - physiopathology
Kidney Transplantation
Male
Mice
Warm Ischemia - methods
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Summary:One of the cornerstone research models used in our laboratories is the induction of ischemic injury through cold ischemia followed by warm ischemia to donor kidneys to mimic the clinical realities of transplantation. The experimental design of the present study included bilateral nephrectomies on the day of syngeneic kidney transplant, with serum creatinine measured 24 hours postoperatively to measure acute function. Cold ischemia time in these experiments was always 30 minutes, and warm ischemia time was not standardized but always recorded. It became apparent that some transplanted kidneys that should have displayed injury were producing close to normal serum creatinine levels on postoperative day 1. In reviewing our data, we found a potential correlation between warm ischemia time and serum creatinine, in particular a significant proportion of low serum creatinine results (0.48 ± 0.26 mg/dL vs 1.99 ± 1.11 mg/dL; P < .05) was associated with warm ischemia times that were significantly shorter than our historical average (29.2 ± 2.7 min vs 35.7 ± 2.2 min; P < .05). The kidneys with lower serum creatinine also displayed lower apoptosis and brush border injury scores and fewer tubular casts. Therefore, we concluded that establishing a minimum warm ischemia time was just as important as standardized cold ischemia time to ensure consistent injury in this model. •Consistent injury models are required to investigate intervention modalities.•Warm ischemia is a part of the ischemia-reperfusion injury cascade.•Warm ischemia and cold ischemia can be considered as separate events.
ISSN:0041-1345
1873-2623
DOI:10.1016/j.transproceed.2020.08.010