Optimizing low-dose rituximab protocol for ABO-mismatched kidney transplantation: long-term outcomes in a...

ABO-mismatched kidney transplantation (KTx) expands donor availability but increases risks of antibody-mediated rejection and passenger lymphocyte syndrome (PLS). While rituximab (Rit) potentially mitigates these complications, conventional high-dose regimens (375 mg/m²) elevate infectious and hematologic toxicity. We implemented low-dose Rit induction (200 mg/body) for desensitization in minor/major ABO-mismatched and DSA-positive KTx, evaluating its efficacy and safety over 15-years.

This single-center retrospective cohort (May 2009-April 2024) analyzed 161 adult KTx recipients: Rit (n = 107) and Non-Rit (n = 54) groups. All received tacrolimus, mycophenolate mofetil, prednisolone, and basiliximab; high-risk patients also underwent plasmapheresis. Outcomes included graft survival, biopsy-proven acute rejection, de novo donor-specific antibody (DSA) formation, infection, severe neutropenia, and PLS.

1-year graft survival was 100% in both groups. 5-year death-censored graft survival was 95.8% (Rit) vs 95.9% (Non-Rit), respectively (log-rank P = 0.43). Biopsy-proven acute rejection (7.5% vs 3.7%, P = 0.50) and de novo DSA production were equivalent (Class I: 5.5% vs 2.2%; Class II: 6.6% vs 8.7%; both P = 1.00), with lower mean fluorescent intensity (MFI) in the Rit group. Cytomegalovirus disease, urinary tract infection and fungal infection rates were comparable between both groups. Grade 4 neutropenia was not associated with Rit (OR 2.65; 95% CI 0.63-11.0; P = 0.18). Blood transfusion for hemoglobin declines occurred in 5.6% vs 7.4%, with preserved haptoglobin in all cases, indicating no PLS.

Low-dose Rit induction achieves excellent graft survival and effective PLS prevention, without increasing toxicity, supporting its adoption as an optimal desensitization strategy.