AbstractBackgroundHuman‐cytomegalovirus (hCMV) infection involving the gastrointestinal tract represents a leading cause of morbidity and mortality among kidney transplant (KT) recipients (KTRs). Signs and symptoms of the disease are extremely variable. Prompt anti‐viral therapy administration and immunosuppression modification are key factors for optimizing management. However, complex work‐up strategies are generally required to confirm the preliminary diagnosis. Unfortunately, solid evidence and guidelines on this specific topic are not available.We consequently aimed to summarize current knowledge on post‐KT hCMV‐related gastrointestinal disease (hCMV‐GID).MethodsWe conducted a systematic review (PROSPERO ID: CRD42023399363) about hCMV‐GID in KTRs.ResultsOur systematic review includes 52 case‐reports and ten case‐series, published between 1985 and 2022, collectively reporting 311 cases. The most frequently reported signs and symptoms of hCMV‐GID were abdominal pain, diarrhea, epigastric pain, vomiting, fever, and GI bleeding. Esophagogastroduodenoscopy and colonoscopy were the primary diagnostic techniques. In most cases, the preliminary diagnosis was confirmed by histology. Information on anti‐viral prophylaxis were extremely limited as much as data on induction or maintenance immunosuppression. Treatment included ganciclovir and/or valganciclovir administration. Immunosuppression modification mainly consisted of mycophenolate mofetil or calcineurin inhibitor minimization and withdrawal. In total, 21 deaths were recorded. Renal allograft‐related outcomes were described for 26 patients only. Specifically, reported events were acute kidney injury (n = 17), transplant failure (n = 5), allograft rejection (n = 4), and irreversible allograft dysfunction (n = 3).ConclusionsThe development of local and national registries is strongly recommended to improve our understanding of hCMV‐GID. Future clinical guidelines should consider the implementation of dedicated diagnostic and treatment strategies.