The Role of Rituximab in ABO-Compatible Renal Transplantation: A Comprehensive Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background and Objectives: Rituximab, a monoclonal antibody targeting CD20+ B-cells, is used in autoimmune diseases and B-cell malignancies. Recently, rituximab has been used as an induction agent in kidney transplantation. Our study evaluates the efficacy of rituximab induction on biopsy-proven acute rejection (BPAR), patient survival, and graft survival in ABO-compatible patients. Materials and Methods: A systematic literature search was performed across five databases, following PRISMA guidelines, and the protocol was registered in PROSPERO (CRD42024603984). The inclusion criteria consisted of randomized controlled trials (RCTs), exploring the impact of rituximab induction on eligible kidney transplant recipients with BPAR, graft, and patient survival as the primary outcomes. Risk ratios (RR) with 95% confidence intervals (CI) were estimated by the random-effects model. The risk of bias was assessed via the Cochrane ROB-2 tool across five domains. Results: From an initial 859 potentially relevant studies, three RCTs, including 454 patients, met the inclusion criteria. At 6 months, rituximab was associated with a non-significant reduction in the risk of BPAR (RR 0.76; 95% CI, 0.50–1.15; I2 = 0%). Similarly, patient survival remained unchanged at 6 months (RR 1.01; 95% CI, 0.98–1.04; I2 = 0%). Due to significant heterogeneity, long-term outcomes were assessed using narrative synthesis, which revealed no additional benefit for rituximab in terms of graft or patient survival. Furthermore, potential safety concerns—especially in terms of infection risk—were noted. The certainty of this evidence was low, due to clinical heterogeneity in the included studies causing very serious indirectness. Conclusions: Induction with rituximab provides no significant benefit over standard regimens. Thus, its routine use in ABO-compatible renal transplants may not be justified. The available evidence is of low certainty. Further trials are needed before drawing a firm conclusion and to determine the best dosage, timing, and combinations.