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Is a single low-fixed dose of rituximab sufficient for treating acute humoral rejection after kidney transplantation?

Rituximab has been used to treat acute humoral rejection (AHR) after kidney transplantation. However, the optimal dosing of rituximab is still unknown. Recently, Mulley et al. (1) reported the outcome of seven kidney-transplant patients who developed a refractory AHR, which were treated initially by plasma exchange (PE) (n 12) and intravenous immunoglobulins (IVIg; total administrated dose was 1.2 g/kg). In case of persistence of histologic features of AHR on a kidney biopsy performed 4 weeks after having started this therapy, a single dose of rituximab (500 mg) was given. After a median follow-up of 20 (8.8–32.4) months, patientandgraftsurvivalswere100%.Overall, serum creatinine level was significantly decreased compared with the peak of serum creatinine level reached during the rejection. Finally, only 3 of the 7 patients developed an infectious complication. The authors suggest that a single dose of rituximab may be sufficiently efficient to treat AHR, with few adverse events and significant cost savings (1). However, we wonder whether these impressive results are really attributable to the single rituximab infusion. Indeed, before rituximab infusion, serum creatinine level had decreased in all patients compared with the peak reached during the acute rejection episode. However, after the rituximab infusion, serum creatinine level continued its decrease in three patients; whereas in the four remaining patients it increased or remained stable until last follow-up. In our previously published pilot study on eight kidney-transplant patients presenting AHR, we had found that treating with PE, rituximab (375 mg/m weekly for 3–5 consecutive weeks) with or without T-cell depleting agents was associated with a graft survival of 75% after a median follow-up of 8 (6–30) months (2). We have recently updated our series and found that treating 22 kidney-transplant patients with the same protocol was associated with a graft survival of 77.3% after a median follow-up of 9 (2– 48) months (3). In our previous two studies, infection rate was respectively of 50% and 86.4%, whereas it was only 43% in the study by Mulley et al. The difference in the infectious complication rates observed between the two protocols is probably due to the lack of use of T-cell depleting agents and to the use of IVIg in the study by Mulley et al. As suggested in the later study, these infections cannot be solely attributed to rituximab as patients received a wide range of immunosuppression. T-cell depleting agent, as well as tacrolimus trough levels and mycophenolate mofetil doses which are not mentioned at all in the Mulley et al. study play a major role in the observed infectious complications in this setting, especially that most of these infections are T-cell mediated. In this setting, immunosuppressants targeting T-cells should be used with caution to avoid infections. We acknowledge that the use of IVIg after PE and rituximab may be useful for preventing infections. In conclusion, unfortunately the study by Mulley et al. does not allow establishing the optimal dosing of rituximab for treating AHR. Further prospective study was still required.