4.7 Article

Cold Saline Perfusion before Ischemia-Reperfusion Is Harmful to the Kidney and Is Associated with the Loss of Ezrin, a Cytoskeletal Protein, in Rats

Journal

BIOMEDICINES
Volume 9, Issue 1, Pages -

Publisher

MDPI
DOI: 10.3390/biomedicines9010030

Keywords

organ preservation; acute kidney injury; cold perfusion; cytoskeleton; ezrin

Funding

  1. Hungarian Research Fund: OTKA-ANN (FWF) [110810]
  2. Academy of Finland [131255, 218021, 255551]
  3. Helsinki Biomedical Graduate Program (AAW)
  4. Bolyai Research Scholarship of the Hungarian Academy of Sciences
  5. Merit Prize of Semmelweis University
  6. Kispal Gyula startup grant of the University of Pecs [300021]
  7. OTKA [SNN 114619]
  8. [EFOP-3.6.3-VEKOP-16-2017-00009]

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The study reveals that perfusion with ice-cold saline can cause more severe injury than ischemia-reperfusion at body temperature. Saline independently causes serious injury, while preservation solutions are more beneficial especially at 4 degrees Celsius. Therefore, using preservation solutions in kidney transplantation can help improve ischemic recovery.
Background: Organ protection for transplantation is perfusion with ice-cold preservation solutions, although saline is also used in animal experiments and living donor transplantations. However, ice-cold perfusion can contribute to initial graft injury. Our aim was to test if cytoskeletal damage of parenchymal cells is caused by saline itself or by the ice-cold solution. Methods: F344 rat kidneys were flushed with cold (4 degrees C) saline, ischemic and sham kidneys were not perfused. In a separate set, F344 kidneys were flushed with saline or preservation solution at 4 or 15 degrees C. Ischemia time was 30 min. Results: Renal injury was significantly more severe following cold ischemia (CI) than after ischemia-reperfusion without flushing (ischemia/reperfusion (I/R)). Functional and morphologic damage was accompanied by severe loss of ezrin from glomerular and tubular epithelial cells after CI. Moreover, saline caused serious injury independently from its temperature, while the perfusion solution was more beneficial, especially at 4 degrees C. Conclusions: Flushing the kidney with ice-cold saline can cause more severe injury than ischemia-reperfusion at body temperature even during a short (30 min) ischemia. Saline perfusion can prolong recovery from ischemia in kidney transplantation, which can be prevented by using preservation solutions.

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