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 microg/L; epidermal growth factor, 10 microg/L; insulin-like growth factor-1, 10 microg/L] during cold storage with UW lactobionate solution. Dogs transplanted with kidneys stored for 4days in TFS-UW had significantly lower peak serum creatinine values (mean 2.9 +/- 0.2mg/dL) and returned to normal values faster (6 days) than kidneys stored for 3days in unmodified UW solution (4.2 +/- 0.3 mg/dL and 14 days, respectively). Kidneys stored for 5days in TFS-UW (mean peak creatinine 3.7 +/- 0.3) functioned equivalently to kidneys stored for 3days and better than kidneys stored for 4 days in UW alone. Dogs with kidneys stored for 6days 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 4days in UW alone (20days 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.