Infection-Associated Allograft Inflammation Mimicking Acute Cellular Rejection: A Case of Spontaneous Resolution with Targeted Antimicrobial Therapy

Introduction: Differentiating true acute rejection from infection-mediated allograft inflammation is challenging in transplant nephrology. Current histological classification system fails to distinguish infection driven inflammation from rejection. This case illustrates biopsy-proven Banff 2A acute cellular rejection resolving with prolonged antimicrobial therapy, without needing enhanced immunosuppression, challenging conventional management approaches. Case Description: A 53-year-old female, known diabetic underwent a living-donor kidney transplant. She had low level DSA to DQ1 necessitating additional dose of Rituximab to standard Induction therapy. She had a stormy early postoperative course with perinephric fluid collection needing drain placement, Clostridium difficile diarrhea, and renal vein stenosis needing endovascular stenting and therapeutic anticoagulation, all of which caused slow graft function. A month later, she developed perinephric abscess and MRSA bacteremia requiring rehospitalization. A biopsy on week six revealed a Banff 2A acute cellular rejection. She ended up with a prolonged course of targeted ertapenem therapy. Due to the active infection, her rejection was treated with steroids only and her immunosuppression was tailored to monotherapy despite being 2 months posttransplant. The patient showed progressive renal function improvement, with creatinine decreasing from 4.2 mg/dL to 1.8 mg/dL. A follow-up biopsy confirmed complete resolution of rejection features. Discussion: This case highlights the diagnostic challenge where infection-mediated inflammation mimics acute rejection, despite differing pathophysiology. Managing immunosuppression in the setting of infection is often a dilemma advocating for a cautious approach. Multidisciplinary care involving nephrology, transplant surgery, and infectious disease teams are crucial. This case also emphasizes recognizing infection as a significant mimicker of acute rejection and supports initiating antimicrobial therapy before escalating immunosuppression in actively infected recipients. In individualized cases, modified rejection management strategies with less aggressive immunosuppression may be warranted while actively treating ongoing infection.