Rituximab is not a “magic drug” in post-transplant recurrence of nephrotic syndrome

Abstract

Pediatric patients with end-stage renal failure due to severe drug-resistant nephrotic syndrome are at risk of rapid recurrence after renal transplantation. Treatment options include plasmapheresis, high-dose of cyclosporine A/methylprednisolone and more recently—rituximab (anti-B CD20 monoclonal depleting antibody). We report five patients with immediate (1–2 days) post-transplant recurrence of nephrotic syndrome, treated with this kind of combined therapy including 2–4 weekly doses of 375 mg/m2 of rituximab. Only two (of five) patients have showed full long-term remission, while the partial remission was seen in two cases, and no clinical effect at all was achieved in one patient. The correlation between B CD19 cells depletion and clinical effect was present in two cases only. Severe adverse events were present in two patients, including one fatal rituximab-related acute lung injury.Conclusion: The anti-CD20 monoclonal antibody may be not effective in all pediatric cases of rapid post-transplant recurrence of nephrotic syndrome, and benefit/risk ratio must be carefully balanced on individual basis before taking the decision to use this protocol. What is Known: • nephrotic syndrome may recur immediately after renal transplantation • plasmapheresis combined with pharmacotherapy is used as rescue management • rituximab was reported as effective drug both in primary and post-transplant nephrotic syndrome What is New: • rituximab may not be effective is several cases of post-transplant nephrotic syndrome due to variety of underlying mechanisms of the disease, which may be or not be responsive to this drug • there may be no correlation between drug-induced depletion of specific B cells and clinical effect; this might suggest B-cell independent manner of rituximab action

Efficacy and Safety of rituximab in children with difficult-to-treat nephrotic syndrome; a systematic review

“…Then, we reviewed full-text of selected articles and removed 49 studies because the topics were not relevant to the subject. Finally, 17 investigations were included in the systematic review (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). The flow diagram of study selection is shown in Figure 1.…”

“…Continued decrease the use of immunosuppressants and steroid. Only one study concluded that RTX might not be effective in all pediatric cases of rapid post-transplant recurrence of NS, and they suggested that before deciding to use this protocol, the ratio of benefit to risk should carefully be balanced on an individual basis (10). In this systematic review, 17 studied were included, but only two of them were randomized clinical trials (most of them were retrospective studies without control groups), hence we could not do a quantitative synthesis (metaanalysis).…”

Ofatumumab in post‐transplantation recurrence of a pediatric steroid‐resistant idiopathic nephrotic syndrome

“…Rituximab has been reported to be effective in SRNS, although not in our patient, as proteinuria was only slightly decreased, and this was in association with IAds. Prior reports have also indicated that rituximab is not always successful with post‐transplantation recurrence of SRNS …”

“…Prior reports have also indicated that rituximab is not always successful with post-transplantation recurrence of SRNS. 10 Abatacept, which is an inhibitor of the T-cell costimulatory molecule B7-1, has led to a complete remission in some rituximab-resistant post-transplantation NS. 11 IAds were stopped for our patient during the abatacept infusions, although it soon became apparent that the proteinuria increased and reached nephrotic levels, thus confirming IAds-dependency.…”

Tolerance in Kidney Transplantation: What Is on the B Side?

“…To hamper this process, an anti-CD20 B cell depleting monoclonal antibody, rituximab, has been introduced as immunosuppressive treatment for transplanted patients. Despite the fact that the use of this drug has increased patients' survival, it fails to induce chronic unresponsiveness to the graft [39, 40]. One of the possible reasons underneath may be that plasmablasts and plasma cells, two key players in chronic rejection, do not express CD20 on their cell surface.…”