Summary: Repeated or persistent acute rejection episodes (AR) can lead to chronic rejection (CR). Antibody-mediated rejection (AMR); T cell-mediated rejection (TCMR) and mixed variants (MV), are considered the main cause of graft loss (GL), challenging the management of immunosuppressive therapy (IT). Reinforcing IT with a four-drug (4D) regimen that includes m-TOR inhibitors (m-TORi), calcineurin inhibitors (CNI), mycophenolate (MF) and steroids could be a good strategy in this scenario. However, there is no consensus on this matter. We present our experience with 4D in kidney transplant (KT) recipients who presented CR or recurrent episodes of AR.
Objectives: To evaluate at 3, 6 and 12 months the kidney graft function (KF),histological features and the safety of 4D in kidney transplant recipients (KR) that present CR or repeated AR. 
Materials and Methods:19 kidney transplant (KT) patients treated with 4D from 2008 to 2022 were included. KF was evaluated with eGFR by CKD-EPI equation in addition to the urinary protein/creatinine ratio (PCR) at 0 or baseline, 3, 6 and 12 months. Data recorded: Histological diagnosis by which 4D was initiated, number of acute rejections pre and after starting 4D and histological findings after the start of 4D; Donor specific antibodies (DSA) pre 4D, at the time of change to 4D and post initiation of 4D with Luminex® technique; Incidence and prevalence of BK virus (BKV), infectious events (IE) and neoplastic events (NE) after the start of 4D. 
Results: Statistical analysis was performed using IBM® SPSS® software. Mean age was 47.6 ± 12.8 years, 42.1% were women.100% of patients had at least one episode of acute TCMR, AMR or MV before being converted to a 4D regimen. The eGFR was 40 (27-63) ml/min, 44 (30-60) ml/min, 51 (31-59) ml/min, 48 (31-64) ml/min pre 4D, at 3, 6 and 12 months respectively (p=0.662). The PCR was 138 (100-336) ug/g, 132 (0-197) ug/g, 115 (0-159) ug/g, 157 (45-495) ug/g pre 4D, a 3, 6 and 12 months respectively (p=0.662). The percentage of DSA at the time of transplant was 10.5%, 42.5% at the time of change of IS and 53.3% after starting 4D (p=0.522). Index biopsies, and follow up biopsies were analyzed on a patient-by patient basis as shown in table 1. Post 4D, 4 patients presented BR, 1 patient presented a TCMR IB, one patient presented a TCMR IA and the rest did not present acute episodes.47.4% (n=9) of patients presented an infectious episode. BK viruria pre-4D was 5.6%, and post-4D was 11.1% (p=0.556).There were no neoplastic events recorded in this cohort.There were 2 GL and only one patient discontinued the 4D regimen due to intolerance. There were 3 deaths with a functioning graft (15.8%), all due to infectious causes. GL without censoring death was 15.8%.
Conclusion: KT recipients switched 4D stabilized their eGFR and PCR; no new DSA were found; There was no evidence of a higher incidence of BK virus or neoplastic events.