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This study examined the effect of trophic factor supplementation [TFS; bovine neutrophil peptide-1 (bactenecin), 1 mg/L; substance P, 2.5 mg/L; nerve growth factor, 20 μg/L; epidermal growth factor, 10 μg/L; insulin-like growth factor-1, 10 μg/L] during cold storage with UW lactobionate solution. Dogs transplanted with kidneys stored for 4 days in TFS-UW had significantly lower peak serum creatinine values (mean 2.9 ± 0.2 mg/dL) and returned to normal values faster (6 days) than kidneys stored for 3 days in unmodified UW solution (4.2 ± 0.3 mg/dL and 14 days, respectively). Kidneys stored for 5 days in TFS-UW (mean peak creatinine 3.7 ± 0.3) functioned equivalently to kidneys stored for 3 days and better than kidneys stored for 4 days in UW alone. Dogs with kidneys stored for 6 days in TFS-UW had mean peak creatinines of 5.7 ± 0.4 mg/dL. These returned to normal creatinine values in 14 days, equal to 3-day stored and significantly better than kidneys stored for 4 days in UW alone (20 days recovery time). This study shows trophic factor deprivation appears to be a critical mechanism of injury in organ preservation with current synthetic storage media, and marks the initial development of a synthetic biologically active preservation solution, the next generation of preservation media.