Chronic renoprotective effect of pulsatile perfusion machine RM3 and IGL-1 solution in a preclinical kidney transplantation model

J Transl Med. 2012 Nov 21:10:233. doi: 10.1186/1479-5876-10-233.

Abstract

Background: Machine perfusion (MP) of kidney graft provides benefits against preservation injury, however decreased graft quality requires optimization of the method. We examined the chronic benefits of MP on kidney grafts and the potential improvements provided by IGL-1 solution.

Method: We used an established autotransplantation pig kidney model to study the effects of MP against the deleterious effects of warm ischemia (WI: 60 minutes) followed by 22 hours of cold ischemia in MP or static cold storage (CS) followed by autotransplantation. MPS and IGL-1 solutions were compared.

Results: Animal survival was higher in MPS-MP and both IGL groups. Creatinine measurement did not discriminate between the groups, however MPS-MP and both IGL groups showed decreased proteinuria. Chronic fibrosis level was equivalent between the groups. RTqPCR and immunohistofluorescent evaluation showed that MP and IGL-1 provided some protection against epithelial to mesenchymal transition and chronic lesions. IGL-1 was protective with both MP and CS, particularly against chronic inflammation, with only small differences between the groups.

Conclusion: IGL-1 used in either machine or static preservation offers similar levels of protection than standard MP. The compatibility of IGL-1 with both machine perfusion and static storage could represent an advantage for clinical teams when choosing the correct solution to use for multi-organ collection. The path towards improving machine perfusion, and organ quality, may involve the optimization of the solution and the correct use of colloids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Chronic Disease
  • Cryopreservation
  • Epithelial-Mesenchymal Transition / drug effects
  • Fibrosis
  • Inflammation / pathology
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney / physiopathology
  • Kidney Transplantation*
  • Models, Animal*
  • Multivariate Analysis
  • Organ Preservation Solutions / pharmacology*
  • Phenotype
  • Protective Agents / pharmacology*
  • Pulsatile Flow*
  • Recovery of Function / drug effects
  • Reverse Transcriptase Polymerase Chain Reaction
  • Survival Analysis
  • Swine

Substances

  • Biomarkers
  • IGL-1 solution
  • Organ Preservation Solutions
  • Protective Agents