Steroid pulse therapy for acute T-cell-mediated rejection after kidney transplantation: mechanisms, evidence, and unresolved questions.

Intravenous methylprednisolone (MP) pulse therapy remains the standard first-line treatment for acute T-cell-mediated rejection following kidney transplantation. However, the dose and duration of this therapy were established empirically more than three decades ago rather than by contemporary rigorous dose-finding trials. The most common treatment regimens consist of 250-500 mg MP daily for three to five days, but substantial between-center variability persists. This narrative review explores the historical development of steroid pulse dosing, the available comparative clinical data, and the biological rationale underlying current practice. The commonly used dose range of 250-500 mg daily for three to five days rests largely on historical convention rather than on contemporary dose-finding evidence. A series of small prospective and randomized studies failed to demonstrate superior efficacy of more intensive regimens when compared with doses broadly resembling current practice. Mechanistically, glucocorticoids act through genomic and rapid non-genomic pathways, supporting a hypothesis-generating dose-window concept rather than a simple linear dose-response model. Contemporary data further indicate that clinical response does not reliably predict histologic resolution and that MP pulse rejection treatment carries significant toxicity. Overall, steroid pulse therapy remains biologically plausible and clinically entrenched; however, the optimal dose and duration have yet to be established under current tacrolimus- and mycophenolate-based immunosuppression. More precise response monitoring will also be required to develop more effective and less toxic treatment regimens.