Kidney transplantation is the preferred treatment for patients with end-stage kidney
disease. Maintaining organ viability between donation and transplantation, as well
as minimizing ischemic injury, are critically important for long-term graft function
and survival. Moreover, the increasing shortage of transplantable organs is a considerable
problem; thus, optimizing the condition of grafts is a pivotal task. Here, rodent
models of kidney transplantation and cold storage were used to demonstrate that supplementation
of a preservation solution with Sigma-1 receptor (S1R) agonist fluvoxamine (FLU) reduces
cold and warm ischemic injury. Post-transplant kidney function was improved, histological
injury was mitigated, and mRNA expression of two tubular injury markers—kidney injury
molecule-1 and neutrophil gelatinase-associated lipocalin—was robustly reduced. In
addition, renal inflammation was diminished, as shown by reduced leukocyte infiltration
and pro-inflammatory cytokine expression. In the cold ischemia model, FLU ameliorated
structural injury profoundly after 2 h as well as 24 h. The reduced number of TUNEL-positive
and Caspase 3-positive cells suggests the anti-apoptotic effect of FLU. None of these
beneficial effects of FLU were observed in S1R−/− mice. Of note, organ damage in FLU-treated
kidneys after 24 h of cold storage was similar to just 2 h without FLU. These results
indicate that S1R agonists can prolong storage time and have great potential in improving
organ preservation and in alleviating the problem of organ shortages.
