Trophic factor and FR167653 supplementation during cold storage rescue chronic renal injury

Abstract

Purpose: The use of organs from deceased after cardiac death and extended criteria donors grew in the last decade. These organs are more sensitive to ischemia-reperfusion injury during transplantation and current preservation protocols do not protect them adequately.

Materials and methods: In an autotransplanted, deceased after cardiac death donor pig kidney model we evaluated the benefits of supplementation with University of Wisconsin solution trophic factors and FR167653, an inhibitor of p38 mitogen-activated protein kinase.

Results: Supplemented solution improved renal recovery and limited ischemia-reperfusion injury, particularly when agents were used in conjunction. Long-term benefits were highlighted by decreased renal fibrosis, as determined by Picrosirius staining, and inflammation, as evaluated by renal cell infiltration. Mechanistic evaluation showed decreased expression of epithelial-to-mesenchymal transition markers, a process involved in renal fibrosis development. Tumor necrosis factor-α was markedly decreased in the treated experimental group. Apoptosis was also decreased, accompanied by decreased p38 mitogen-activated protein kinase phosphorylation.

Conclusions: Supplementing the current gold standard kidney preservation protocol with trophic factors and p38 mitogen-activated protein kinase inhibitors markedly increased the quality of grafts in our pig deceased after cardiac death donor model. Hence, this represents a strategy of interest to improve transplantation outcomes.