Cold ischemia and the reduced long-term survival of cadaveric renal allografts

BACKGROUND: Prolonged cold ischemia time (CIT) is accompanied by delayed cadaveric renal allograft function and early allograft loss, but the effect of CIT on long-term allograft survival is less certain and has not been studied in detail. METHODS: Using data from the United Network for Organ Sharing, we identified 6465 patients who received a kidney-only transplant of cadaveric origin for the first time in 1995. We examined the effect of CIT on the 6-year survival of these kidneys using Cox proportional hazard analysis. RESULTS: The mean CIT of the kidney was 21 +/- 7 hours (mean +/- SD) and correlated with the serum creatinine on discharge (R= 0.20, P < 0.001) and the distance traveled by the kidneys (R= 0.30, P < 0.001). CIT had a significant effect on the 6-year allograft survival (a 10-hour increase in CIT was associated with a hazard risk ratio (RR) of 1.20 for graft failure (P < 0.001) that persisted (RR = 1.40, P= 0.021) after adjusting for donor age, recipient age and race, human leukocyte antigen (HLA) mismatch, panel reactive antibodies, and first 6 months' rejection treatments. Similarly, compared to CIT category of 0 to 10 hours, the 6-year graft survival was progressively worse for 11 to 20 hours (RR = 1.03), 21 to 30 hours (RR = 1.12), and, significantly so, for >30 hours (RR = 1.32; P= 0.011). The gain in HLA match with increasing CIT was not uniform; for instance, HLA match in >30 hours was lower than for 21 to 30 hours (2.4 +/- 1.5 vs. 2.7 +/- 1.6; P < 0.001). CONCLUSION: (1) Cadaveric kidneys continue to undergo prolonged periods of cold ischemia; (2) prolonged cold storage is associated with longer distance traveled by the kidneys, but is not associated with any significant gain in tissue matching; and (3) prolonged cold ischemia is a significant predictor of long-term graft loss. Reducing prolonged cold ischemia by regional distribution of organs and less stringent tissue matching may reduce the persistent high rate of long-term loss of cadaveric renal allografts.