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.