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


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.
Institut national de la santé et de la recherche médicale U927, Faculté de Médecine et Pharmacie, University of Poitiers, and Département de Biochimie, Centre Hospitalier Universitaire de Poitiers, Poitiers, France.
Thibault
T
Desurmont
Sebastien
S
Giraud
Jerome
J
Cau
Jean-Michel
JM
Goujon
Michel
M
Scepi
Jerome
J
Roumy
Nicolas
N
Chatauret
Raphael
R
Thuillier
Thierry
T
Hauet
D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D005978:Glutathione / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D016030:Kidney Transplantation; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D011887:Raffinose / Q000494:pharmacology; D013552:Swine; D014022:Tissue Survival / Q000187:drug effects*
C104334:FR 167653; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins; D019188:Organ Preservation Solutions; D011720:Pyrazoles; D011725:Pyridines; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose