A Case of Epstein-Barr Virus–Associated Transplanted Kidney Post-Transplant Lymphoproliferative Disorder Complicated by Hemophagocytic Lymphohistiocytosis, Six Years after Transplantation

INTRODUCTION: We present a case of acute kidney failure due to post-transplant lymphoproliferative disorder (PTLD) in the transplanted kidney 6 years after transplantation. Epstein-Barr virus (EBV) infection was identified as the likely trigger, and reducing immunosuppression was sufficient to resolve both inflammation and renal failure. CASE PRESENTATION: A female patient in her twenties with acute renal failure had undergone a living-donor kidney transplantation from an EBV-positive donor, who was her mother, 6 years earlier and continued to receive immunosuppressive medication, including tacrolimus, everolimus, mycophenolate mofetil, and methylprednisolone. The patient was negative for EBV antibodies before transplantation but had become positive after 6 months, despite no detectable EBV DNA in her blood. Her creatinine (CRE) level had remained stable at around 1.5 mg/dL, but suddenly rose to 2.0 mg/dL at 6 years after transplantation. Graft rejection was suspected, and steroid pulse treatment was performed, but this did not improve renal function, while fever, thrombocytopenia, and hemolytic anemia appeared. Thrombotic microangiopathy (TMA) was suspected, so tacrolimus and everolimus were discontinued and mycophenolate mofetil was increased. However, transplant kidney biopsy showed no findings of TMA. Therefore, these findings were suspected to be symptoms of hemophagocytic lymphohistiocytosis (HLH). PCR testing revealed EBV viremia, and the patient was diagnosed with EBV-associated HLH. CRE rose to 6.0 mg/dL but gradually decreased after changing immunosuppressive drugs, and the patient's fever resolved. Staining of the kidney biopsy with Epstein-Barr virus encoded RNA (EBER) was positive for infiltrated lymphocytes, leading to the diagnosis of PTLD. No other lesions, such as enlarged lymph nodes, were observed on imaging. Since her symptoms resolved, she has been under outpatient observation with mycophenolate mofetil and methylprednisolone without additional treatment. Her blood EBV nucleic acid level did not increase, and CRE has remained stable at 1.6 mg/dL. CONCLUSIONS: In a rare case, HLH developed during immunosuppressive treatment of acute renal failure suspected to represent graft rejection. It then was diagnosed as EBV-induced late PTLD instead, and the patient's condition improved and stabilized after immunosuppressant regimen adjustment. We recommend regular EBV-monitoring and consideration of the possibility of graft PTLD in similar cases.