The implications of acute rejection for allograft survival in contemporary U.S. kidney transplantation

BACKGROUND: We examined the frequency and clinical impact of acute rejection (AR) in contemporary U.S. kidney transplantation. METHODS: Data for Medicare-insured kidney transplant recipients in 2000 to 2007 (n=48,179) were drawn from the United States Renal Data System. AR events were ascertained from Organ Procurement and Transplantation Network reports. AR was subclassified as antibody (Ab)-treated AR or other management (non-Ab-treated AR). Associations of AR with subsequent all-cause graft loss were estimated with time-varying Cox regression. Covariates included recipient, donor, and transplant factors in the United Network for Organ Sharing Kidney Allocation Review Committee survival model. RESULTS: The frequencies of non-Ab-treated AR per 100 graft-years at risk among standard criteria donor recipients over the first 6, 12, 24, and 36 months after transplantation were 9.93, 8.43, 5.71, and 4.70, respectively. Non-Ab-treated AR was consistently more than twice as common as Ab-treated AR by risk period and donor type. Development of Ab-treated AR predicted a greater risk of graft loss than non-Ab-treated AR. The relative risk for graft loss from Ab-treated AR continuously increased with later timing of AR after transplantation, whereas risk associated with non-Ab-treated AR peaked for events reported in months 13 to 24 after kidney transplantation. Regardless of the diagnosis time, the relative risk of graft loss was higher in the first 89 days after a given AR report compared with 90 days and beyond. CONCLUSIONS: AR events recognized later after transplantation have more serious graft loss implications, especially within the first 89 days after AR reporting. This observation may reflect reduced intensity of monitoring, delays in diagnosis, or clinicopathologic features of late AR.