Graft-vs.-Host Disease Following Simultaneous Liver-Kidney Transplantation: A Diagnostic Challenge in a Kidney Transplant Recipient

Introduction: Graft-versus-host disease (GVHD) is rare following solid organ transplantation and poses a unique diagnostic challenge for nephrologists and transplant providers. Its symptoms can overlap with drug reactions, infections, or acute rejection, and delayed recognition may lead to poor outcomes. We describe a case of GVHD after simultaneous liver-kidney transplantation (SLKT), an increasingly common procedure where GVHD remains an exceptionally rare complication. Case Description: A 55-year-old woman with MASH cirrhosis and hepatorenal syndrome underwent SLKT on April 4, 2025, from a DCD donor (KDPI 59%). She had 0% PRA, did not receive induction immunosuppression, and experienced immediate graft function. Her initial recovery was uneventful. On post-op day 23, she developed fatigue, poor appetite, a diffuse erythematous rash, and acute kidney injury with a creatinine of 3.78 mg/dL. Renal function improved with volume resuscitation, but systemic symptoms persisted. Skin biopsy showed vacuolar interface dermatitis with necrotic keratinocytes. Duodenal and rectosigmoid biopsies revealed crypt apoptosis, glandular distortion, and crypt abscess formation. CD3+ T-cell chimerism analysis from peripheral blood showed 45% donor cells, confirming significant donor T-cell engraftment and supporting a diagnosis of GVHD. Given the extent of organ involvement and biopsy findings, she was made NPO and started on high-dose intravenous methylprednisolone and ruxolitinib. Over the following days, she demonstrated clinical improvement, including resolution of rash and normalization of renal function. Discussion: GVHD is a rare but serious complication of SLKT. Diagnosis can be delayed due to overlapping features with other post-transplant conditions. This case highlights the importance of maintaining a high index of suspicion in patients with compatible symptoms. The integration of histopathology with peripheral blood chimerism was essential to timely diagnosis and management. Early initiation of immunosuppression may improve outcomes in this rare transplant complication.