Abstract
BackgroundAcute kidney allograft rejection is a major cause for declining graft function and has a negative impact on the long-term graft survival. The majority (90%) of acute rejections are T-cell mediated and, therefore, the anti-rejection therapy targets T-cell-mediated mechanisms of the rejection process. However, there is increasing evidence that intragraft B-cells are also important in the T-cell-mediated rejections. First, a significant proportion of patients with acute T-cell-mediated rejection have B-cells present in the infiltrates. Second, the outcome of these patients is inferior, which has been related to an inferior response to the conventional anti-rejection therapy. Third, treatment of these patients with an anti-CD20 antibody (rituximab) improves the allograft outcome as reported in single case observations and in one small study. Despite the promise of these observations, solid evidence is required before incorporating this treatment option into a general treatment recommendation.Methods/DesignThe RIACT study is designed as a randomized, double-blind, placebo-controlled, parallel group multicenter Phase III study. The study examines whether rituximab, in addition to the standard treatment with steroid-boli, leads to an improved one-year kidney allograft function, compared to the standard treatment alone in patients with acute T-cell mediated tubulointerstitial rejection and significant B-cell infiltrates in their biopsies. A total of 180 patients will be recruited.DiscussionIt is important to clarify the relevance of anti-B cell targeting in T-cell mediated rejection and answer the question whether this novel concept should be incorporated in the conventional anti-rejection therapy.Trial registrationClinical trials gov. number: NCT01117662
Highlights
Acute kidney allograft rejection is a major cause for declining graft function and has a negative impact on the long-term graft survival
It is important to clarify the relevance of anti-B cell targeting in T-cell mediated rejection and answer the question whether this novel concept should be incorporated in the conventional anti-rejection therapy
Even if renal allograft function returns to baseline values after anti-rejection therapy this may reflect some degree of compensatory hyperfiltration and obscure the loss of nephrons and development of interstitial fibrosis and tubular atrophy (IF/ TA) [5]
Summary
High dose steroid therapy is standard-of-care for treating acute T-cell mediated rejection of renal allografts, along with intensified maintenance immunosuppressive therapy in some cases (KDIGO-Guidelines [1]). Only one pilot study examined the effect of rituximab in the treatment of biopsy-proven acute T-cell mediated rejection with B-cell infiltrates [13]. Despite the promise of the cited studies [13,18] critical evaluation invariably leads to the conclusion that the evidence is not sufficient to treat acute transplant rejection with rituximab. This includes the small number of reported cases, short follow-up periods and heterogeneity of inclusion criteria, and the histological grading in these studies. The acronym RIACT–study stands for a multi-center randomized placebo controlled double blind study to test the efficacy of RItuximab in Acute Cellular tubulointerstitial rejection with B-cell infiltrates in renal Transplant patients (RIACT)
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