Establishment of Murine Model of Kidney Failure Induced by Severe Ischemia-Reperfusion Injury Useful to Evaluate Transplantation and Regenerative Therapies

Transplant Proc. 2020 May;52(4):1202-1205. doi: 10.1016/j.transproceed.2020.02.014. Epub 2020 Mar 10.

Abstract

Background: Severe ischemia-reperfusion injury (SIRI) seems to be the key factor that can significantly affect the function of both native kidneys and renal allografts. Therefore, the development of a successful strategy is of a paramount importance in both basic and clinical research.

Methods: To determine the effects of SIRI on the native kidney function, a murine model was planned as follows: group 1 (n = 6) mice underwent to nephrectomy plus ischemia-reperfusion injury for 30 minutes; group 2 (n = 6) mice underwent to nephrectomy without ischemia-reperfusion injury and thus served as sham controls for SIRI. The results of serum creatinine (SCr) were analyzed using Mann-Whitney U tests to calculate the significance between mean values. Survival between groups was measured by Kaplan-Meier test.

Results: To reliably achieve an elevation of SCr levels animals were exposed to a SIRI. The values of SCr increased from 0.35 (SD, 0.09) mg/dL to about 2-fold within 2 days and 3-fold within the following 5 days. Under these given conditions the mice displayed signs and histologic findings of severe kidney damage. The survival rate was about 83% of the animals within a week, and they showed no capacity of complete spontaneous self-regeneration.

Conclusions: In this study, we aim to establish a murine model with extensive structural kidney damage and significant elevation of SCr levels, which could be used in basic and translational research of transplantation and regenerative therapies.

MeSH terms

  • Animals
  • Creatinine / blood
  • Disease Models, Animal*
  • Kidney / physiopathology
  • Kidney Transplantation*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Renal Insufficiency / etiology*
  • Renal Insufficiency / pathology
  • Renal Insufficiency / physiopathology
  • Reperfusion Injury / complications*
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology

Substances

  • Creatinine