Refractory Antibody-mediated Rejection Research Articles

Long term tolerability and clinical outcomes associated with tocilizumab in the treatment of refractory antibody mediated rejection (AMR) in pediatric renal transplant recipients.

Treatment options for antibody-mediated rejection (AMR) are limited. Recent studies have shown that inhibition of interleukin-6 (IL-6)/interleukin-6 receptor (IL-6R) signaling can reduce inflammation and slow AMR progression. We report our experience using monthly tocilizumab (anti-IL6R) in 25 pediatric renal transplant recipients with AMR, refractory to IVIg/Rituximab. From January 2013 to June 2019, a median (IQR) of 12 (6.019.0) doses of tocilizumab were given per patient. Serial assessments of renal function, biopsy findings, and HLA DSA (by immunodominant HLA DSA [iDSA] and relative intensity score [RIS]) were performed. Median (IQR) time from transplant to AMR was 41.4 (24.367.7) months, and time from AMR to first tocilizumab was 10.6 (8.317.6) months. At median (IQR) follow up of 15.8 (8.435.7) months post-tocilizumab initiation, renal function was stable except for 1 allograft loss. There was no significant decrease in iDSA or RIS. Follow up biopsies showed reduction in peritubular capillaritis (p=.015) and C4d scoring (p=.009). The most frequent adverse events were cytopenias. Tocilizumab in pediatric patients with refractory AMR was well tolerated and appeared to stabilize renal function. The utility of tocilizumab in the treatment of AMR in this population should be further explored.

Clinicopathologic Characteristics of Late Acute Antibody-mediated Rejection in Pediatric Liver Transplantation.

An early and accurate diagnosis of liver antibody-mediated rejection (AMR) followed by timely intervention is important for clinical management but remains challenging. The aim of this study was to assess the clinicopathologic characteristics and outcomes of late acute AMR in pediatric liver transplantation recipients. We performed a retrospective review of 739 ABO-identical/compatible allograft liver biopsies from 199 pediatric transplantation recipients. Based on Banff 2016 AMR criteria, 3 recipients fulfilled the criteria for definite for late acute AMR, 2 met the criteria for suspicious for AMR, and 2 were indeterminate for AMR. We further assessed the clinicopathologic characteristics of these 7 patients. All 7 patients had at least 1 biopsy with a histopathologic pattern compatible with acute AMR. Additionally, we observed accompanied moderately to markedly dilated portal/central veins and endothelialitis disproportionate to the degree of bile duct injury in all 7 patients; periportal/perivenular hepatocyte necrosis was seen in 6 of 7 patients; and arteritis was seen in 3 of 7 patients. In each case, microvascular C4d deposition was present in at least 1 biopsy. Posttransplant donor specific anti-HLA antibodies were detected in 5 patients. Two of 7 patients were retransplanted, and 2 died after developing refractory AMR. The remaining 5 patients were alive with stable graft function at a median follow-up of 4.1 years. Our data suggest that acute AMR in pediatric liver grafts is rare, can develop late, and may be associated with graft loss or patient death. The recurrent histopathologic findings of moderately to markedly dilated portal/central veins and endothelialitis disproportionate to the degree of bile duct injury are features that appear unique to pediatric acute AMR of liver grafts.

Incidence, risk factors, treatment, and consequences of antibody-mediated kidney transplant rejection: A systematic review.

Antibody-mediated rejection (AMR) is a leading cause of kidney allograft failure, but its incidence, risk factors, and outcomes are not well understood. We searched Ovid MEDLINE, Cochrane, EMBASE, and Scopus from January 2000 to January 2020 to identify published cohorts of ≥500 incident adult or 75 pediatric kidney transplant recipients followed for ≥1year post-transplant. At least two reviewers screened 5061 articles and abstracts; 28 met inclusion criteria. Incidence of acute AMR was 1.1%-21.5%; most studies reported 3%-12% incidence, usually within the first year post-transplant. Few studies reported chronic AMR incidence, from 7.5%-20.1% up to 10 years. Almost all patients with acute or chronic AMR received corticosteroids and intravenous immunoglobulin; most received plasmapheresis, and approximately half with rituximab. Most studies examining death-censored graft failure identified AMR as an independent risk factor. Few reported refractory AMR rates or outcomes, and none examined costs. Most studies were single-center and varied greatly in design. Cohort studies of kidney transplant recipients demonstrate that AMR is common and associated with increased risk of death-censored graft failure, but studies vary widely regarding populations, definitions, and reported incidence. Gaps remain in our understanding of refractory AMR, its costs, and resulting quality of life.

Daratumumab as Salvage Therapy in Pediatric Thoracic Organ Transplantation: An Addition to the Antibody Mediated Rejection Toolbox?

Purpose Antibody mediated rejection (AMR) is difficult to treat and often results in death or graft loss. Therapies targeted at antibodies or B cells are inadequate for decreasing donor specific antibodies (DSA), particularly to MHC class II. Bortezomib, a small molecule proteasome inhibitor targets plasma cells, but has many side effects and unsatisfactory results. Alternatively, we used Daratumumab (DAR), an anti-CD38 monoclonal antibody, in two pediatric transplant (Tx) recipients. Methods Chart review. Results An 18-year-old female with cystic fibrosis had a lung-liver Tx at 12-years-old. Twenty months post-Tx she developed severe AMR and Acute cellular rejection (ACR) treated with ATG, rituximab, TPE, photopheresis, and steroids. She ultimately required redo lung Tx. She did well for three years, but then developed AMR. She again received TPE, ATG, photopheresis, and rituximab. She was not considered a candidate for third lung Tx so all attempts were made to salvage her graft. She had no B cells, but continued to make DSA, so a plasma cell targeted therapy was desired. She received three doses of DAR 16 mg/kg on days 0, 7 and 21 with no infusion reactions. She developed neutropenia 2 months later which resolved with 3 weeks of GCSF. Both total PRA and DSA significantly decreased after DAR and have not returned 7 months later. PRA class I dropped from peak of 96% to 0, class II from peak 34% to 3%. She is maintained on subcutaneous IgG replacement for secondary hypogammaglobulinemia. Her graft function is poor, but has stabilized since DAR. She had one episode of presumed line associated sepsis and MSSA pneumonia without sequalae. A 3-year-old girl two years post heart Tx developed refractory AMR (by C4d and elevated DSA) despite ATG, TPE, IVIG, eculizumab, and ofatumumab. She then received two doses of DAR, 16 mg/kg each on days 0 and 14. She tolerated the infusions without any initial side effects. Not enough time has elapsed to follow up antibody levels or graft function. Conclusion Treatment for AMR remains challenging, especially when due to class II HLA antibodies. We safely administered DAR to two pediatric patients without infusion reactions or significant infectious complications to date. One patient had a decline in antibodies, while the other is too soon to determine. While more studies are needed, DAR may be a promising addition to the AMR toolbox.

Eculizumab for Treatment of Biopsy Negative Rejection in Heart Transplantation

Introduction Antibody mediated rejection (AMR) may be suspected in Heart Transplant (HT) patients with biopsy negative rejection (BNR). Donor specific antibodies (DSA) can support this diagnosis. Molecular phenotyping of endomyocardial biopsies (EMB) has identified rejection associated transcripts which correlate with decreased left ventricular ejection fraction (EF) but not with AMR on EMB. BNR may respond to augmented immunosuppression. Thus, there is evidence that BNR may represent rejection. The pathophysiology of AMR involves complement activation. Eculizumab, a monoclonal antibody targeting C5a treats AMR in renal transplant patients. We present two cases of eculizumab use for BNR with presumed AMR in HT patients. Case Report A 22 year old male underwent HT in 2007 for non-ischemic cardiomyopathy (NICM). His post-operative course was complicated by grade 2 AMR and mild cardiac allograft vasculopathy (CAV1) with normal graft function. In 2018 he presented with EF 20%. Coronary angiography (CA) showed CAV1. EMB and DSA were negative. Following treatment for presumed AMR with steroids, IVIG, therapeutic plasma exchange (TPE) and extracorporeal photopheresis (ECP), EF improved to 54%. Three months later he developed symptomatic graft dysfunction (EF 35%). EMB, DSA were negative. CA was stable. Cardiac magnetic resonance imaging (MRI) showed mid myocardial late gadolinium enhancement (LGE). He underwent empiric AMR treatment, with addition of eculizumab. EF normalized with sustained improvement at 18 months. He is maintained on monthly ECP and eculizumab. Our second patient is a 27 year old male with HT in 2009 for NICM. He had recurrent cellular and AMR with re-transplantation in 2013 for recalcitrant CAV. In 2017 he presented in cardiogenic shock, EF 35%. CA showed CAV1. EMB showed grade 1 CMR, negative for AMR. Class I DSA was positive, low level MFI (1053). He was treated with steroids, TPE, IVIG and thymoglobulin. EF further declined to 25%. MRI showed subendocardial inferior LGE. Eculizumab was commenced. Side effects included mild headaches. EF normalized at 6 months. He continues with biweekly ECP and eculizumab. Summary In our patients with BNR and presumed refractory AMR, eculizumab resulted in improved graft function. Research is needed into the efficacy, dosing and duration of therapy. Eculizumab is a therapeutic prospect for HT patients with presumed AMR and BNR.

Modest Improvements in Refractory Antibody-Mediated Rejection After Prolonged Treatment

Active and chronic active antibody-mediated rejection (ABMR) are major causes of allograft loss after kidney transplantation.1 There is no standard treatment approach for ABMR, but intravenous immunoglobulin (IVIG), steroids, and targeted B-cell therapies have been found to have relative success in reducing allograft injury and preserving function.2–4,S1 In contrast, outcomes for patients with refractory or resistant, chronic active ABMR (cABMR) are generally poor with limited success reported with the addition of bortezomib, eculizumab, or IVIG and rituximab to the standard of care.

Risk Factors and Outcomes of Acute and Refractory Antibody-Mediated Rejection

Risk Factors and Outcomes of Acute and Refractory Antibody-Mediated Rejection

Bortezomib Against Refractory Antibody-Mediated Rejection After ABO-Incompatible Living-Donor Liver Transplantation: Dramatic Effect in Acute-Phase?

Antibody-mediated rejection (AMR) is a refractory rejection after donor-specific antibody-positive or ABO blood-type incompatible (ABOi) organ transplantation. Rituximab dramatically improved the outcome of ABOi living-donor liver transplantation (LDLT); however, an effective treatment for posttransplant AMR, once occurred, is yet to be established. A 44-year-old woman with biliary cirrhosis underwent ABOi-LDLT from her sister (AB-to-A). Pretransplant rituximab diminished CD19/20-positive B lymphocytes to 0.6%/0.0%; however, AMR occurred on posttransplant day-6 with marked increase in both CD19/20 cells (17.1%/5.8%) and anti-B IgM/G-titers (1024/512). Despite rituximab readministration, steroid-pulse, intravenous immunoglobulin, and plasmapheresis, AMR was uncontrollable, with further increasing CD19/20 cells (23.0%/0.0%) and antibody-titers (2048/512). Bortezomib (1.0 mg/m2) was thus administered on posttransplant day-9, immediately ameliorating CD19/20 cells (1.3%/0.0%) and antibody-titers (<256/128). Complete remission of refractory AMR was obtained by just 2 doses of bortezomib. Her liver function has been stable thereafter for over 3 years. This case highlighted the efficacy of bortezomib against refractory AMR after ABOi-LDLT. Unlike previous reports, the efficacy was very dramatic, presumably due to the administration timing near the peak of acute-phase AMR.

Daratumumab in Sensitized Kidney Transplantation: Potentials and Limitations of Experimental and Clinical Use.

Donor-specific antibodies are associated with increased risk of antibody-mediated rejection and decreased allograft survival. Therefore, reducing the risk of these antibodies remains a clinical need in transplantation. Plasma cells are a logical target of therapy given their critical role in antibody production. To target plasma cells, we treated sensitized rhesus macaques with daratumumab (anti-CD38 mAb). Before transplant, we sensitized eight macaques with two sequential skin grafts from MHC-mismatched donors; four of them were also desensitized with daratumumab and plerixafor (anti-CXCR4). We also treated two patients with daratumumab in the context of transplant. The animals treated with daratumumab had significantly reduced donor-specific antibody levels compared with untreated controls (57.9% versus 13% reduction; P<0.05) and prolonged renal graft survival (28.0 days versus 5.2 days; P<0.01). However, the reduction in donor-specific antibodies was not maintained because all recipients demonstrated rapid rebound of antibodies, with profound T cell-mediated rejection. In the two clinical patients, a combined heart and kidney transplant recipient with refractory antibody-mediated rejection and a highly sensitized heart transplant candidate, we also observed a significant decrease in class 1 and 2 donor-specific antibodies that led to clinical improvement of antibody-mediated rejection and to heart graft access. Targeting CD38 with daratumumab significantly reduced anti-HLA antibodies and anti-HLA donor-specific antibodies in a nonhuman primate model and in two transplant clinical cases before and after transplant. This supports investigation of daratumumab as a potential therapeutic strategy; however, further research is needed regarding its use for both antibody-mediated rejection and desensitization.

Bortezomib Treatment for Refractory Antibody-Mediated Rejection Superimposed with BK Virus-Associated Nephropathy during the Progression of Recurrent C3 Glomerulonephritis

Wonseok Do, M.D., Jong-Hak Lee, M.D., Kyung Joo Kim, M.D., Man-Hoon Han, M.D., Hee-Yeon Jung, M.D., Ji-Young Choi, M.D., Sun-Hee Park, M.D., Yong-Lim Kim, M.D., Chan-Duck Kim, M.D., Jang-Hee Cho, M.D., Youngae Yang, M.D., Minjung Kim, M.D., Inryang Hwang, M.D., Kyu Yeun Kim, M.D., Taehoon Yim, M.D.,<span style=

The Effect of Bortezomib on the Management of Immediate Postoperative Refractory Antibody-Mediated Rejection after Kidney Transplantation

The Effect of Bortezomib on the Management of Immediate Postoperative Refractory Antibody-Mediated Rejection after Kidney Transplantation

Refractory Antibody-Mediated Rejection in Kidney-Pancreas Transplant

Refractory Antibody-Mediated Rejection in Kidney-Pancreas Transplant

Eculizumab for Treatment of Refractory Antibody-Mediated Rejection in Kidney Transplant Patients: A Single-Center Experience

Antibody-mediated rejection (AMR) is responsible for up to 20%–30% of acute rejection episodes after kidney transplantation. In several cases, conventional therapies including plasmapheresis, intravenous immunoglobulin, and anti-CD20 therapy can resolve AMR successfully. But in some cases the load of immunoglobulins that can activate complement cascade may submerge the routine desensitization therapy and result in the formation of membrane attack complexes. Eculizumab, a monoclonal antibody against C5, was reported to be an option in cases with severe AMR that are resistant to conventional therapy. Here, we present 8 cases that were resistant to conventional therapy and in which eculizumab was given as a salvage treatment. Given the bad prognosis for renal transplants displaying acute injury progressing rapidly to cortical necrosis on the biopsy, the prompt use of eculizumab could have the advantage of immediate effects by stopping cellular injury. This can provide a therapeutic window to allow conventional treatment modalities to be effective and prevent early graft loss.

The Effect of Bortezomib on Antibody-Mediated Rejection after Kidney Transplantation.

PurposeRecently, bortezomib has been used to treat antibody-mediated rejection (AMR) refractory to conventional treatment such as plasmapheresis, intravenous immunoglobulin, and rituximab. The authors aimed to describe their experiences when bortezomib was used to treat refractory AMR.Materials and MethodsEleven refractory AMR episodes treated with bortezomib were included in this study. The patients received one or two cycles of bortezomib (1.3 mg/m2) on days 1, 4, 8, and 11.ResultsBortezomib effectively reduced antibodies against various targets, including human leukocyte antigen (HLA) class I and II, ABO blood group antigen, and angiotensin II type 1 receptor. Antibodies were depleted or reduced significantly in eight AMR episodes. Overall, there was a significant improvement in the mean estimated glomerular filtration rate (eGFR) at 3 months after therapy (36.91±22.15 mL/min/1.73 m2) versus eGFR at time of AMR diagnosis (17.00±9.25 mL/min/1.73 m2; p=0.007). All six early-onset AMR episodes (within 6 months post-transplantation) showed full recovery of allograft function. Additionally, three of the five late-onset AMR episodes (>6 months post-transplantation) showed improved allograft function.ConclusionAnti-humoral treatment based on bortezomib might be an effective strategy against refractory AMR caused by various types of antibodies. Notably, this treatment could be more effective in early-onset AMR than in late-onset AMR.

The Impact of Toll-Like Receptor Signaling On B Cells Responding to Blood Group A Carbohydrates.

[Aim] Bacterial infection following ABO-incompatible organ transplantation has been reported to be associated with refractory antibody-mediated rejection targeting blood type antigens. In this study, we investigated the influence of toll-like receptor(TLR) signaling, through the binding of bacterial-derived ligands, on B cell activation in response to blood group carbohydrate-antigens. [Methods] We have previously demonstrated that B cells responding to blood group A-antigens differentiate into CD11+CD5+B-1a cells, which can be blocked by calcineurin inhibitor(CsA) treatment, in mice, resembling humans. Resting B cells isolated from the splenocytes of Balb/c mice were treated with anti-IgM F(ab), an analog of TI-2 Ags, in the presence or absence of lipopolysaccharide(LPS)(10μg/ml) and CsA in vitro. After 3 days in culture, the phenotypic alteration of proliferating B-cells was analyzed by flow cytometry. Balb/c mice were also immunized with human blood type A-erythrocytes, with or without LPS administration(1 or 10μg/mouse). [Results] CD19+B cells stimulated with anti-IgM F(ab) proliferated vigorously. The proliferating B cells differentiated into CD5+B-1a cells in the absence of LPS, but in the presence of LPS, they differentiated into CD5-B-1b cells. A clinically relevant concentration of CsA(100ng/mL) completely blocked B-1a differentiation, but did not affect B-1b cell differentiation. Consistent with our previous findings, B-cells with anti-A receptors showed an sIgM+CD5+B-1a phenotype in mice immunized with A-erythrocytes. However, those cells showed an sIgM+CD5dim/-B-1b phenotype in mice immunized with A-erythrocytes together with LPS. Anti-A antibody production was augmented by LPS dose-dependently. CsA-treatment significantly inhibited anti-A Ab production in response to immunization with A-erythrocytes, though not in mice treated with LPS. [Conclusions] To our knowledge, these data provide the first evidence that B-cells responding to blood type A carbohydrate, in the presence of TLR signaling, show the sIgM+CD5dim/-B-1b phenotype, and lose susceptibility to inhibition by CsA. Blocking TLR signaling in B-cells with anti-A receptors may be a novel strategy to regulate Ab-mediated rejection associated with bacterial infection, following transplantation.

Treatment of Refractory Antibody-mediated Rejection with Bortezomib in a Kidney Transplant Recipient: A Case Report

Antibody-mediated rejection (ABMR) is associated with poor renal allograft survival. It shows poor response to conventional treatment with plasmapheresis, rituximab, and intravenous immunoglobulin. Bortezomib, a proteasome inhibitor used for treatment of multiple myeloma, has recently been reported as a treatment alternative for recipient desensitization and ABMR. A 58-year-old man was diagnosed with mixed-type ABMR with donor specific antibodies and acute T cell-mediated rejection early after kidney transplantation. Conventional therapy was administered, including antithymocyte globulin, plasmapheresis, and rituximab; however, his condition was found to be refractory to these antihumoral therapies. Following administration of bortezomib, his serum creatinine level returned to baseline with stable graft function. His serum creatinine level remains stable at 1.3 mg/dL at 10 months posttransplantation. Bortezomib is effective for treatment of refractory ABMR following kidney transplantation.

Late antibody-mediated rejection in renal allografts: outcome after conventional and novel therapies.

Although several strategies for treating early antibody-mediated rejection (AMR) in kidney transplants have been investigated, evidence on treatment of late AMR manifesting after 6 months is sparse. In this single-center series, we present data on 23 consecutive patients treated for late AMR. Late AMR was diagnosed using Banff 2007 criteria along with presence of donor-specific antibodies (DSA) and acute rise in serum creatinine (SCr). Response to therapy was assessed by improvement in SCr, histologic improvement, and decline in DSA strength. Overall, 17% (4/23) had documented nonadherence while 69% (16/23) had physician-recommended reduction in immunosuppression before AMR. Eighteen patients (78%) were treated with plasmapheresis or low-dose IVIg+rituximab; 11 (49%) with refractory AMR also received one to three cycles of bortezomib. While there was an improvement (P=0.02) in mean SCr (2.4 mg/dL) at the end of therapy compared with SCr at the time of diagnosis (2.9 mg/dL), this improvement was not sustained at most recent follow-up. Eleven (48%) patients had no histologic resolution on follow-up biopsy. Lack of histologic response was associated with older patients (odds ratio [OR]=3.17; P=0.04), presence of cytotoxic DSA at time of diagnosis (OR=200; P=0.04), and severe chronic vasculopathy (cv≥2) on index biopsy (OR=50; P=0.06). A major setting in which late AMR occurred in our cohort was reduction or change in immunosuppression. Our data demonstrate an inadequate response of late AMR to current and novel (bortezomib) therapies. The benefits of therapy need to be counterweighed with potential adverse effects especially in older patients, large antibody loads, and chronic allograft vasculopathy.

Proteasome Inhibitor Based Protocol For Antibody Mediated Rejection In Kidney Transplantation

Background Rapid and complete elimination of donor-specific anti-human leukocyte antigen antibodies (DSA) during antibody-mediated rejection (AMR) of renal transplantation is rarely achieved with traditional antihumoral therapies. Current antihumoral therapies do not target the mature antibody producing plasma cells. Bortezomib is a first in class proteosome inhibitor for the treatment of plasma cell derived tumors like multiple myeloma. Proteasome inhibitor-based therapy has been shown to effectively treat refractory AMR. Here, we report on our experience with plasma cell targeted therapy (bortezomib) as an antirejection strategy for refractory early and delayed AMR post renal transplantation. Methods Adult kidney transplant recipients with AMR, diagnosed by Banff criteria, received a bortezomib-based regimen after failing at least 2 traditional treatments for AMR. Bortezomib therapy was administered (1.3 mg/m2 IV D1,4,8,11) with plasmapheresis performed immediately before each dose of Bortezomib and a single dose of rituximab (375 mg/m2) given with the first bortezomib dose. Methylprednisolone was administered along with Bortezomib at 100 mg IV on D1,4 and 50 mg IV on D8,11. All patients received valganciclovir prophylaxis for prevention of herpes zoster and cytomegalovirus reactivation. Monitoring included serial donor-specific antihuman leukocyte antigen antibody (DSA) levels, serum creatinine levels, urine protein excretion and repeated allograft biopsies. Results Ten episodes of AMR in eight renal transplant recipients were treated with bortezomib, rituximab, methylprednisone and plasmapheresis. Post treatment reduction in immunodominant DSA was observed and this data will be available at the meeting. None of the patients experienced peripheral neuropathy from bortezomib and only one patient had GI toxicity with nausea and diarrhea, which was transient. None of the patients had reactivation of herpes zoster infection. In conclusion, bortezomib, rituximab, methylprednisone and plasma exchange therapy provided reversal of AMR rejection post renal transplantation with improvement in renal function, proteinuria and histology, at a median follow-up of 15 months. Disclosures: No relevant conflicts of interest to declare.

Acute antibody-mediated rejection after lung transplantation

Antibody-mediated rejection (AMR) after lung transplantation remains enigmatic, and there is no consensus on the characteristic clinical, immunologic and histologic features. We performed a retrospective, single-center cohort study and identified cases of acute AMR based on the presence of circulating donor-specific human leukocyte antigen (HLA) antibodies (DSA), histologic evidence of acute lung injury, C4d deposition and clinical allograft dysfunction. We identified 21 recipients with acute AMR based on the aforementioned criteria. AMR occurred a median 258 days after transplantation; 7 recipients developed AMR within 45 days of transplantation. All patients had clinical allograft dysfunction, DSA, histology of acute lung injury and capillary endothelial C4d deposition. Fifteen recipients improved clinically and survived to hospital discharge, but 6 died of refractory AMR. One survivor had bronchiolitis obliterans syndrome at the time of AMR diagnosis; 13 of the 14 remaining survivors developed chronic lung allograft dysfunction (CLAD) during follow-up. Overall, 15 recipients died during the study period, and the median survival after the diagnosis of AMR was 593 days. Acute AMR can be a fulminant form of lung rejection, and survivors are at increased risk of developing CLAD. The constellation of acute lung injury, DSA and capillary endothelial C4d deposition is compelling for acute AMR in recipients with allograft dysfunction. This clinicopathologic definition requires validation in a multicenter cohort, but may serve as a foundation for future studies to further characterize AMR.

Eculizumab for Salvage Treatment of Refractory Antibody-Mediated Rejection in Kidney Transplant Patients: Case Reports

Antibody-mediated rejection (AMR) in a group of preoperatively desensitized patients may follow a dreadful course and result in loss of the transplanted kidney. In several cases, conventional therapies including plasmapheresis, intravenous immunoglobulin, and anti-CD 20 therapy can resolve AMR successfully. But in some cases the load of immunoglobulins that can activate complement cascade may submerge the routine desensitization therapy and result in the formation of membrane attack complexes. Eculizumab, monoclonal antibody against C5, was reported to be an option in cases with severe AMR that are resistant to conventional therapy. Here, we present two cases of acute-onset AMR in preoperatively desensitized patients. Eculizumab was used as a salvage agent in addition to conventional therapy. Given the bad prognosis for renal transplants displaying acute injury progressing rapidly to cortical necrosis on the biopsy, the prompt use of eculizumab could have the advantage of immediate effects by stopping cellular injury. This can provide a therapeutic window to allow conventional treatment modalities to be effective and prevent early graft loss.