*Purpose: To evaluate the efficacy and safety of a protocol increasing the net state of immunosuppression for adult kidney transplant recipients (KTR) with delayed graft function (DGF).

*Methods: Single-center retrospective cohort of adult KTR with DGF transplanted from January 2017 to March 2021. Pre- vs post-DGF protocol implementation outcomes were evaluated. Protocol included cumulative 6 mg/kg rabbit antithymocyte globulin (rATG) induction, non-weight-based mycophenolate mofetil dosing (1000 mg bid), and higher goal tacrolimus trough (9-12 ng/mL). Pre-protocol patients received cumulative 4.5 mg/kg rATG. Efficacy outcomes were biopsy proven acute rejection (BPAR) and graft loss at 6 months. Safety outcomes were incidence of cytopenia, infection, and all-cause readmission at 6 months.

*Results: Eighty-nine DGF patients met inclusion criteria. Baseline characteristics were similar between groups, with median age (57±19) years and majority Hispanic (42.7%) males (61.8%) with a negative crossmatch (100%). Most post-protocol patients received 6 mg/kg cumulative rATG induction (71.4%) and mycophenolate mofetil 1,000 mg bid (80.3%) with therapeutic tacrolimus troughs by discharge (64.3%). Significantly less BPAR was observed post-protocol (7/56, 12.5% vs 10/33, 30.3%; p = 0.04). Of those with BPAR, significantly less post-protocol patients experienced T-cell mediated rejection (TCMR) than pre-protocol (2/7, 28.6% vs 9/10, 90.0%; p = 0.03). However, antibody-mediated (4/7, 57.1% vs 1/10, 10%) and mixed (1/7, 14.3% vs 0%) rejection were more frequent post-protocol (p = 0.10 and 0.41, respectively). Graft loss was similar post- vs pre-protocol (5/56, 8.9% vs 0; p = 0.16). All post-protocol graft losses were due to death (4 from COVID-19 and 1 unknown). Safety outcomes were similar between groups (Table 1).

*Conclusions: An increased net state of immunosuppression in DGF KTR significantly lowered the 6-month incidence of BPAR without significantly affecting safety. TCMR incidence was significantly decreased, but displaced by antibody-mediated and mixed rejection, implying need to conduct further prospective studies of larger sample sizes. Given majority of graft losses were due to COVID-19 pneumonia, studies are needed to evaluate the risk of COVID-19 infections in DGF KTR, especially with the availability of vaccines.

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