Introduction: Persistent or repeated episodes of acute rejection (AR) may lead to chronic allograft damage. Antibody-mediated rejection (AMR); T-cell mediated rejection (TCMR) and mixed variants (MR) of chronic kidney allograft rejection (CR) are nowadays considered as the main causes of graft loss (GL). This encompasses from endothelial damage up to fibrosis challenging immunosuppressive therapy (IT) management. IT reinforcement with a four-drug scheme (4D) including m-TOR inhibitors, anticalcineurinics, mycophenolate and steroids, could be a good strategy in this scenario, nevertheless there is no consensus about it. We present our experience with 4D in kidney transplant recipients (KT) That presented with CR or recurrent episodes of AR.

Objectives: To evaluate kidney graft function (KGF), incidence of rejection and safety of a 4D in KT with CR or recurrent episodes of AR.

Methods: KT on treatment with 4D from 2008 to 2021 were included.KGF was evaluated by  estimated glomerular filtration rate with CKD-EPI (eGFR) and urinary  protein/creatinine ratio (PCR)  at 3, 6 and 12 months. Kidney biopsies and panel reactive antibodies (PRA) by Luminex were performed before and after introduction of 4D. BK virus (BKV) incidence, infectious (IE) and neoplastic (NE) events were recorded during the follow up.

Results: 16 KT (median age 45 ± 11 years) were treated with 4D during 52.8 (17-106) months. 43.8% of them were women, 50% were deceased KT. The median post transplant time was 108 (60-129) months. Reasons for 4D introduction were CR in 87.4% of the cases (MR 50%; TCMR 31.3%;  AMR 6.3%) and in the remaining 12, 6%, recurrent or persistent acute TCMR. Median eGFR was 42 (27-66); 44 (31-62); 48 (33-60) and 48 (32-65) ml/min prior to IT change, at 3, 6 and 12 months respectively. At baseline, mean PCR was 179 (147-664) mg/g without significant changes during follow up. Biopsy proven AR was found in 37% of KT under 4D. No NE were registered. 43% of the patients presented a non major IE, and only one patient was BKV positive during follow up with 4D. There was one GL, one loss of follow up and one death due to sepsis with functioning graft.

Conclusions: KT patients with CR or recurrent episodes of AR changed to 4D IT stabilized their renal function and proteinuria. The incidence of new biopsy proven AR was 37% , and no new DSA were found or serious adverse events reported during follow-up. 4D could be a good option to halt the progression of renal damage due to rejection in KT.