*Purpose: Acute rejection (AR) has been shown to impact graft survival after kidney transplant (KTx), however there is limited data on its impact on long term graft outcomes. We sought to study how this impact has changed over time.

*Methods: Using data from the Organ Procurement and Transplantation Network (OPTN) database, we studied adult (age ≥ 18 years) recipients of an isolated, ABO-compatible, kidney transplant in the period between January 2000 and December 2014. Patients were divided in two groups: AR group and no rejection group (NR), based on the presence of both an AR episode and treatment recorded on the OPTN database at one-year post-KTx. Patients lost to follow-up within one year, or whose rejection status was unknown were excluded. A multivariable Cox’s hazards model was used to evaluate the association between AR and the risk of death-censored graft failure (DCGF). Hazard ratio (HR) and 95% confidence interval (CI) are provided as measures of strength of association and precision, respectively. Results are adjusted for donor age and donor type, recipient age, gender, race and diabetes status at transplant, total HLA mismatches at the A,B,DR loci, calculated panel reactive antibodies, delayed graft function and maintenance immunosuppression at one-year post-KTx. ​

*Results: 154,399 patients were included in the study (60%/40% deceased/living donor); of these 10.3% had AR. There was a decrease in AR over time, from 17.6% in 2000 to 6.0% in 2014. Median follow-up was 7 years. Cumulative incidence of DCGF at 7 years post-KTx was 26.6% in the AR group versus 12.9% in the NR group (HR 1.77, 95% CI 1.71-1.83). AR HR increased over time, from 1.34 (95% CI 1.22-1.47) in 2000 to 3.44 (95% CI 2.32-5.10) in 2014. (Figure 1).

*Conclusions: Despite the steady decline in the prevalence of AR, AR has a clinically significant impact on long term graft survival. This impact has worsened from 2000 to 2014 which suggest AR seen now may be much worse than in the past – likely due to selection of higher immunological risk patients with increased use of induction immunosuppression and a higher proportion of antibody mediated rejection. AR is still a clinically relevant event and strategies to minimize its occurrence are needed to mitigate long-term graft loss.

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