Abstract
BackgroundAntibody-mediated rejection (ABMR) is the main cause of renal allograft loss. The most common treatment strategy is based on plasmapheresis plus the subsequent administration of intravenous immunoglobulin (IVIG). Unfortunately, no approved long-term therapy is available for ABMR. The current study was designed to analyze the effect of various ABMR treatment approaches on allograft survival and to compare treatment effects in the presence or absence of donor-specific antibodies (DSAs).MethodsThis single-center study retrospectively analyzed 102 renal allograft recipients who had biopsy-proven ABMR after transplant. DSA was detectable in 61 of the 102 patients. Initial standard treatment of ABMR consisted of plasmapheresis (PS) or immunoadsorption (IA), followed by a single course of IVIG. In case of nonresponse or recurrence, additional immunosuppressive medications, such as rituximab, bortezomib, thymoglobulin, or eculizumab, were administered. In a second step, persistent ABMR was treated with increased maintenance immunosuppression, long-term therapy with IVIG (more than 1 year), or both.ResultsOverall graft survival among transplant patients with ABMR was <50% after 3 years of follow-up. Compared to the use of PS/IA and IVIG alone, the use of additional immunosuppressive medications had no beneficial effect on allograft survival (p = 0.83). Remarkably, allografts survival rates were comparable between patients treated with the combination of PS/IA and IVIG and those treated with a single administration of IVIG (p = 0.18). Renal transplant patients with ABMR but without DSAs benefited more from increased maintenance immunosuppression than did DSA-positive patients with ABMR (p = 0.01). Recipients with DSA-positive ABMR exhibited significantly better allograft survival after long-term application of IVIG for more than 1 year than did recipients with DSA-negative ABMR (p = 0.02).ConclusionsThe results of our single-center cohort study involving kidney transplant recipients with ABMR suggest that long-term application of IVIG is more favorable for DSA-positive recipients, whereas intensification of maintenance immunosuppression is more effective for recipients with DSA-negative ABMR.
Highlights
Despite all efforts, long-term renal allograft survival is limited to an average of 11 to 15 years [1]
donor-specific antibody (DSA) directed against mismatched human leukocyte antigens (HLA) class I and II attach to the endothelium, triggering complement activation via the classic pathway and inducing Fc gamma receptor–dependent effects on the activation of natural killer cells and macrophages
We found that the application of additional immunosuppressive therapy, such as bortezomib, rituximab, thymoglobulin, or eculizumab, did not achieve better renal allograft survival rates than did standard treatment with PS/IA and intravenous immunoglobulin (IVIG) alone (p = 0.83, Figure 3B)
Summary
Long-term renal allograft survival is limited to an average of 11 to 15 years [1]. Membrane attack complex (MAC) activated by C1q is responsible for inflammation in the vascular endothelium, generating direct irreversible injury of the allograft [3]. Histologic features, such as glomerulitis and peritubular capillaritis, as well as chronic glomerulopathy, indicate endothelial damage. C4d is a specific correlate of complement cascade activation initiated by DSAs. As a degradation product of C4, C4d binds to endothelium [3]; often rendering C4d deposits detectable in biopsy samples from allografts in patients with ABMR [6]. Antibody-mediated rejection (ABMR) is the main cause of renal allograft loss. The current study was designed to analyze the effect of various ABMR treatment approaches on allograft survival and to compare treatment effects in the presence or absence of donor-specific antibodies (DSAs)
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