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

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.