A Case Report of Quinine-Induced Thrombotic Microangiopathy Successfully Treated With Eculizumab.

Drug-induced thrombotic microangiopathy (DITMA) is a life-threatening condition which may be immune or nonimmune mediated. Quinine is the most implicated drug in immune-mediated DITMA. However, the optimal treatment is unclear. Complement inhibition by eculizumab has demonstrated success in many DITMA (e.g., carfilzomib, gemcitabine, and tacrolimus), but there are limited data in DITMA, including quinine-associated cases. A 55-year-old female was diagnosed with quinine-associated thrombotic microangiopathy (TMA), as confirmed by a positive quinine-dependent platelet-associated antibody. This was successfully treated with eculizumab with complete resolution of thrombocytopenia and anemia by 1 and 6 weeks. She required hemodialysis for a month and gained full recovery of renal function. We discuss various challenges with the diagnosis and management of DITMA. We also review published data on the use of eculizumab in various DITMA. Our case demonstrates successful treatment of quinine-induced TMA with eculizumab. We recommend further studies to assess the efficacy of complement inhibition in quinine and other DITMA.

Complement-mediated thrombotic microangiopathy treated with anticomplement protein 5 therapy, a retrospective study.

BACKGROUND: Complement-mediated thrombotic microangiopathy (CM-TMA), also called atypical hemolytic uremic syndrome (aHUS), is a difficult-to-diagnose rare disease that carries severe morbidity and mortality. Anti-C5 monoclonal antibodies (aC5-mab) are standard treatments, but large studies and long-term data are scarce. Here, we report our single institution experience to augment the knowledge of CM-TMA treated with aC5-mab therapy. METHODS: We aimed to assess the short and long-term effects of aC5-mab in patients diagnosed with CM-TMA treated outside of a clinical trial. This was a retrospective study. We included all patients diagnosed with CM-TMA and treated with aC5-mab at our institution. There were no exclusion criteria. Endpoints included complete TMA response (CR) defined as normalization of hematological parameters and ≥25% improvement in serum creatinine (Cr) from baseline in patients with renal disease, relapse defined as losing the previously achieved CR, morbidity, adverse events, and survival. RESULTS: We found 28 patients with CM-TMA treated with aC5-mab. The median age was 50 years. Baseline laboratories: platelet counts 93 × 109 /L, hemoglobin 8.6 g/dL, lactate dehydrogenase 1326 U/L, serum Cr 4.7 mg/dL, and estimated glomerular filtration rate 19 mL/min. One individual was on renal replacement therapy (RRT) and 10 initiated RRT within 5 days of the first dose of aC5-mab. Genetic variants associated with CM-TMA included mutations in C3, CFB, CFH, CFHR1/3, CFI, and MCP. The mean duration of hospitalization was 24 days. The median time to initiation of aC5-mab was 10 days. Sixteen subjects received RRT. At the time of hospital discharge, 27 were alive, 14 remained on RRT, and 4 had a CR. At 6 months, 23 patients were alive, 18 continued aC5-mab, 8 remained on RRT, and 9 had a CR. At the last follow-up visit past 6 months, 20 were alive, 14 continued aC5-mab, 5 remained on RRT, 12 had a CR, and 1 was lost to follow-up. CONCLUSIONS: Our study provides real-world experience and insight into the long-term outcomes of CM-TMA treated with aC5-mab. Our findings validate that CM-TMA is an aggressive disease with significant morbidity and mortality, and confirm that aC5-mab is a relatively effective therapy for CM-TMA. Our study adds practical, real-world experience to the literature, but future research remains imperative.

Thrombotic microangiopathy in a patient with anti-signal recognition particle antibody-positive immune-mediated necrotizing myopathy.

We describe the case of a 61-year-old woman with anti-signal recognition particle (SRP) antibody-positive immune-mediated necrotizing myopathy (IMNM) who exhibited biopsy-confirmed thrombotic microangiopathy (TMA). The patient developed proximal-dominant muscle weakness and was diagnosed with anti-SRP antibody-positive IMNM based on muscle biopsy results and serological examination. A high-dose corticosteroid prescription was initiated, followed by intravenous methylprednisolone and intravenous immunoglobulin therapy (IVIg). The patient showed IVIg-induced hemolytic anemia with preserved ADAMTS13 activity. Transient oral tacrolimus administration was initiated. Approximately 8 weeks after admission, the serum creatinine levels gradually increased. Renal histological examination revealed TMA, including ischemic changes in the renal tubules, stenosis, and occlusion of the interlobular arteries with fibrinoid necrosis of the afferent arteriolar walls. The arteriolar walls demonstrated an accumulation of C1q and C3c. Myofiber damage in patients with IMNM accounts for the activation of the classical pathway of the complement cascade in the sarcolemma due to antibody deposition. Additionally, a membrane attack complex is observed on capillaries in the muscle tissues of patients with anti-SRP antibody-positive IMNM. Although drug-induced pathomechanisms, such as IVIg and tacrolimus, can trigger the development of TMA, we suggest that the presence of serum anti-SRP antibodies would be implicated in complement-associated kidney vascular damage.

Eculizumab treatment in paediatric patients diagnosed with aHUS after haematopoietic stem cell transplantation: a HSCT-TMA case series from Japanese aHUS post-marketing surveillance.

Haematopoietic stem-cell transplantation (HSCT)-associated thrombotic microangiopathy (HSCT-TMA) is a serious complication with high mortality. Accumulating evidence suggests that complement dysregulation is potentially involved in the development of HSCT-TMA. We retrospectively analysed the clinical characteristics and outcomes of thirteen paediatric patients who were diagnosed with atypical haemolytic uremic syndrome and treated with eculizumab to manage HSCT-TMA during post-marketing surveillance in Japan. The median time from HSCT to TMA was 31 days (Interquartile range, IQR;21-58) and the median doses of eculizumab was three (IQR;2-5). Seven patients (54%) were alive at the last follow-up while six died due to complications related to HSCT. Six of seven survivors initiated eculizumab after insufficient response to plasma therapy. Following eculizumab treatment, median platelet counts and LDH levels in all survivors significantly improved and renal function improved in 4/7 patients. All survivors possessed potential risk factors of complement overactivation. During the follow-up period after eculizumab discontinuation (median;111.5 days, IQR;95-555), no TMA recurrence was observed. In this analysis, eculizumab showed benefit in over half of this paediatric patient population. Ongoing clinical studies are expected to optimize the treatment regimen of terminal complement pathway inhibitor, and it may become a therapeutic option for paediatric HSCT-TMA in the future.

Emicizumab prophylaxis in infants with hemophilia A (HAVEN 7): primary analysis of a phase 3b open-label trial.

ABSTRACT: Subcutaneous emicizumab enables prophylaxis for people with hemophilia A (HA) from birth, potentially reducing risk of bleeding and intracranial hemorrhage (ICH). HAVEN 7 (NCT04431726) is the first clinical trial of emicizumab dedicated to infants, designed to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab in those aged ≤12 months with severe HA without factor VIII (FVIII) inhibitors. Participants in this phase 3b trial received emicizumab 3 mg/kg maintenance dose every 2 weeks for 52 weeks and are continuing emicizumab during the 7-year long-term follow-up. Efficacy end points included annualized bleed rate (ABR): treated, all, treated spontaneous, and treated joint bleeds. Safety end points included adverse events (AEs), thromboembolic events (TEs), thrombotic microangiopathies (TMAs), and immunogenicity (anti-emicizumab antibodies [ADAs] and FVIII inhibitors). At primary analysis, 55 male participants had received emicizumab (median treatment duration: 100.3; range, 52-118 weeks). Median age at informed consent was 4.0 months (range, 9 days to 11 months 30 days). Model-based ABR for treated bleeds was 0.4 (95% confidence interval, 0.30-0.63), with 54.5% of participants (n = 30) having zero treated bleeds. No ICH occurred. All 42 treated bleeds in 25 participants (45.5%) were traumatic. Nine participants (16.4%) had ≥1 emicizumab-related AE (all grade 1 injection-site reactions). No AE led to treatment changes. No deaths, TEs, or TMAs occurred. No participant tested positive for ADAs. Two participants were confirmed positive for FVIII inhibitors. This primary analysis of HAVEN 7 indicates that emicizumab is efficacious and well tolerated in infants with severe HA without FVIII inhibitors.

Compassionate Use Narsoplimab for Severe Refractory Transplantation-Associated Thrombotic Microangiopathy in Children.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a common and potentially severe complication of hematopoietic cell transplantation. TA-TMA-directed therapy with eculizumab, a complement C5 inhibitor, has resulted in a survival benefit in some studies. However, children with TA-TMA refractory to C5 inhibition with eculizumab (rTA-TMA) have mortality rates exceeding 80%, and there are no other known therapies. Narsoplimab, an inhibitor of the MASP-2 effector enzyme of the lectin pathway, has been studied in adults with TA-TMA as first-line therapy with a response rate of 61%. Although there are limited data on narsoplimab use as a second-line agent in children, we hypothesized, that complement pathways proximal to C5 are activated in rTA-TMA, and that narsoplimab may ameliorate rTA-TMA in children. In this single-center study, children were enrolled on single-patient, Institutional Review Board-approved compassionate use protocols for narsoplimab treatment. Clinical complement lab tests were obtained at the discretion of the treating physician, although all patients were also offered participation in a companion biomarker study. Research blood samples were obtained at the time of TA-TMA diagnosis, prior to eculizumab treatment, at the time of refractory TA-TMA diagnosis prior to the first narsoplimab dose, and 2 weeks after the first narsoplimab dose. Single ELISA kits were used to measure markers of complement activation according to the manufacture's instructions. Five children with rTA-TMA received narsoplimab; 3 were in multiorgan failure and 2 had worsening multiorgan dysfunction at the time of treatment. Additional comorbidities at the time of treatment included sinusoidal obstructive syndrome (SOS; n = 3), viral infection (n = 3), and steroid-refractory stage 4 lower gut grade IV acute graft-versus-host disease (aGVHD, n = 3). Two infants with concurrent SOS and no aGVHD had resolution of organ dysfunction; 1 also developed transfusion-independence (complete response), and the other's hematologic response was not assessable in the setting of leukemia and chemotherapy (partial response). One additional patient achieved transfusion independence but had no improvement in organ manifestations (partial response), and 2 patients treated late in the course of disease had no response. Narsoplimab was well tolerated without any attributed adverse effects. Three patients consented to provide additional research blood samples. One patient with resolution of organ failure demonstrated evidence of proximal pathway activation prior to narsoplimab treatment with subsequent declines in Ba, Bb, C3a, and C5a and increases in C3 in both clinical and research lab tests. Otherwise, there was no clear pattern of other complement markers, including MASP-2 levels, after therapy. In this cohort of ill children with rTA-TMA and multiple comorbidities, 3 patients benefited from narsoplimab. Notably, the 2 patients with resolution of organ involvement did not have steroid-refractory aGVHD, which is thought to be a critical driver of TA-TMA. Additional studies are needed to determine which patients are most likely to benefit from narsoplimab and which markers may be most helpful for monitoring lectin pathway activation and inhibition.

Coronavirus disease 2019-associated thrombotic microangiopathy treated with plasma exchange and antihypertensive therapy in a patient with HIV: A case report with literature review.

RATIONALE: Coronavirus disease 2019 (COVID-19) is an infectious disease that often causes complications in multiple organs and thrombosis due to abnormal blood coagulation. This case report aimed to describe the clinical course of COVID-19-associated thrombotic microangiopathy (TMA) and reviewed the comprehensive information on TMA, thrombotic thrombocytopenic purpura (TTP), and atypical hemolytic uremic syndrome associated with COVID-19 in the past literature. PATIENT CONCERNS: A 46-year-old Japanese man was diagnosed with human immunodeficiency virus infection 10 years ago and treated with antiretroviral therapy. The patient presented with fever, malaise, hematuria, and bilateral upper abdominal discomfort for the past 4 days. DIAGNOSES: COVID-19-associated TMA was diagnosed based on a positive polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 and laboratory findings such as thrombocytopenia, acute kidney injury, and hemolytic anemia. Malignant hypertension and human immunodeficiency virus infection were also considered as differential diagnoses of TMA. INTERVENTIONS: Considering the possibility of TTP, plasma exchange was performed, and glucocorticoids were administered. Hemodialysis was performed for acute kidney injury. Antihypertensive drugs were administered to control the high blood pressure. OUTCOMES: Platelet count and renal function improved, and hemodialysis was no longer required. The patient was in good general condition and was discharged from the hospital. LESSONS: COVID-19-associated TMA should be considered as a differential diagnosis during the COVID-19 epidemic. Excessive inflammation and severe COVID-19 are not essential for TMA development. Early intervention using conventional TMA treatments, such as plasma exchange and corticosteroids, might be important in improving prognosis while differentiating between TTP and atypical hemolytic uremic syndrome. Antihypertensive therapy may be helpful in the treatment of COVID-19-associated TMA.

Studying the Role of C5-Inhibition Therapy in Scleroderma Renal Crisis-Induced Thrombotic Microangiopathy - A Review of Literature.

BACKGROUND: The pathogenesis of scleroderma renal crisis (SRC) remains poorly understood but a growing body of evidence suggests that activation of the complement system may be involved in the disease. Recent studies have shown that Eculizumab (monoclonal antibody directed against the complement component C5) is effective in treating patients with SRC who present with symptoms of thrombotic microangiopathy (SRC-TMA). OBJECTIVES: In this study, we conducted a systematic review to characterize the published experience of the presentation and outcome of patients with SRC who were treated with C5 inhibitor, Eculizumab. METHODS: A literature search was conducted from inception to December 2022 using Medical Subject Headings (MeSH) terms for 'scleroderma', 'scleroderma renal crisis, and 'Eculizumab'. We included case reports, case series, and observational studies which reported the use of Eculizumab with or without Angiotensin-converting enzyme inhibitors (ACE-I) for the treatment of scleroderma renal crisis (SRC) in patients with systemic sclerosis. RESULTS: The study included 17 patients, all of whom were treated with Eculizumab. Additionally, the use of ACE-I was reported in 11/17 (64.7%) patients. Further, plasmapheresis was used in 9/17 (52.9%), steroids in 5/17 (29.4%), cyclophosphamide in 3/17 (17.6%), calcium channel blockers in 3/17 (17.6%), and Rituximab in 3/17 (17.6%) patients. Renal replacement therapy was required in 11/17 (64.7%) patients. 14/17 patients (82.3%) were reported to have clinical (renal or hematologic) improvement with Eculizumab therapy (Table 1). CONCLUSION: These findings should prompt testing on a larger cohort of SRC-TMA patients. This would help us determine whether aggressive treatment combining ACE-I and Eculizumab can target the various underlying endothelial, inflammatory, and immunologic mechanisms involved in SRC-TMA, and improve patient outcomes.

COVID-19 associated thrombotic microangiopathy.

A limited number of cases of thrombotic microangiopathy (TMA) have previously been reported in association with COVID-19. Our report describes two cases of TMA associated with COVID-19, one of which was successfully treated with eculizumab. The first case was a 23-month-old girl, and the second case was a 9-month-old boy. PCR tests for SARS-CoV-2 were positive in both cases, and laboratory results showed microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury. No known aetiology for TMA was found in either case. Stool tests for Shigatoxin-producing Escherichia coli were negative. Coagulation tests, ADAMTS13 activity, serum complement levels, and homocysteine levels were all within the normal range. No known genetic mutation was found, including mutations of complement, diacylglycerol kinase epsilon, and cobalamin C. In the first case, eculizumab was administered due to persistent haemolysis and prolonged anuria. In conclusion, TMA may be associated with COVID-19 infection. Treatment with eculizumab may be beneficial in selected patients because of the potential activation of the complement system.

Snakebite-associated thrombotic microangiopathy: a spotlight on pharmaceutical interventions.

INTRODUCTION: Snakebite is a neglected public health issue causing death and disability, disproportionately affecting tropical and subtropical resource poor countries globally. Snakebite-associated thrombotic microangiopathy (TMA) occurs in a subset of snakebites and is associated with acute kidney injury (sometimes requiring renal replacement therapy) and a risk of chronic kidney disease. AREAS COVERED: This expert review synthesizes current evidence on therapeutic interventions in snakebite-associated TMA via PubMed search for cohort studies and randomized controlled trials (RCTs) in snakebite-associated TMA from 1970 to October 2022. EXPERT OPINION: There are no interventional RCTs in snakebite-associated TMA. Recent cohort studies from Sri Lanka, India, and Australia report clinical and laboratory endpoint outcomes for intervention with antivenom and therapeutic plasma-exchange (TPE). TPE is a resource intense and costly treatment using large volumes of blood donor plasma. There is no consistent evidence supporting TPE in snakebite-associated TMA with respect to patient survival, dialysis-free survival, or hospital length of stay. Antivenom is the standard of care for patients with snake envenoming, but there is no specific evidence of benefit in snakebite-associated TMA. Emerging new therapies in snakebite more broadly are untested in snakebite-associated TMA. RCTs are needed to improve the evidence for treatment of snakebite-associated TMA.

Application of systems biology to identify pharmacological mechanisms of thrombotic microangiopathy evoked by combined activated prothrombin complex concentrate and emicizumab.

Emicizumab is a bispecific monoclonal antibody that substitutes for the function of missing or deficient factor VIII (FVIII) in people with hemophilia A (PwHA). Long-term safety and efficacy of emicizumab have been demonstrated in several clinical trials. Nevertheless, in the first of these, three cases of thrombotic microangiopathy (TMA) occurred in PwHA treated with emicizumab receiving high doses of activated prothrombin complex concentrate (aPCC), a bypassing agent used for treating breakthrough bleeds when FVIII neutralizing antibodies (inhibitors) make FVIII replacement ineffective. The aim of the present work is to offer a method to elucidate the pathophysiological and pharmacological mechanisms involved in this treatment-induced TMA. Systems biology and machine learning-based Therapeutic Performance Mapping System is a validated in silico technology that allowed us to construct models of potential mechanisms behind induced TMA. Two drug combinations were modeled and assessed: emicizumab plus aPCC and emicizumab plus recombinant activated factor VII (another bypassing agent). Our models showed that both combinations were related to activation of the coagulation cascade. However, mechanisms involved mainly in platelet activation and possibly in complement activation were detected only for emicizumab plus aPCC, potentially explaining the occurrence of TMA only in this combination.

MASP2 inhibition by narsoplimab suppresses endotheliopathies characteristic of transplant-associated thrombotic microangiopathy: in vitro and ex vivo evidence.

Transplant-associated thrombotic microangiopathy (TA-TMA) is an endotheliopathy complicating up to 30% of allogeneic hematopoietic stem cell transplants (alloHSCT). Positive feedback loops among complement, pro-inflammatory, pro-apoptotic, and coagulation cascade likely assume dominant roles at different disease stages. We hypothesized that mannose-binding lectin-associated serine protease 2 (MASP2), principal activator of the lectin complement system, is involved in the microvascular endothelial cell (MVEC) injury characteristic of TA-TMA through pathways that are susceptible to suppression by anti-MASP2 monoclonal antibody narsoplimab. Pre-treatment plasmas from 8 of 9 TA-TMA patients achieving a complete TMA response in a narsoplimab clinical trial activated caspase 8, the initial step in apoptotic injury, in human MVEC. This was reduced to control levels following narsoplimab treatment in 7 of the 8 subjects. Plasmas from 8 individuals in an observational TA-TMA study, but not 8 alloHSCT subjects without TMA, similarly activated caspase 8, which was blocked in vitro by narsoplimab. mRNA sequencing of MVEC exposed to TA-TMA or control plasmas with and without narsoplimab suggested potential mechanisms of action. The top 40 narsoplimab-affected transcripts included upregulation of SerpinB2, which blocks apoptosis by inactivating procaspase 3; CHAC1, which inhibits apoptosis in association with mitigation of oxidative stress responses; and pro-angiogenesis proteins TM4SF18, ASPM, and ESM1. Narsoplimab also suppressed transcripts encoding pro-apoptotic and pro-inflammatory proteins ZNF521, IL1R1, Fibulin-5, aggrecan, SLC14A1, and LOX1, and TMEM204, which disrupts vascular integrity. Our data suggest benefits to narsoplimab use in high-risk TA-TMA and provide a potential mechanistic basis for the clinical efficacy of narsoplimab in this disorder.

Hemolytic Uremic Syndrome: A Case Report.

Thrombotic microangiopathy is a pathological condition comprised of microvascular thrombosis involving any body organ leading to thrombocytopenia, coombs-negative hemolytic anemia, and end-organ damage. The clinical presentation of the case shows typical hemolytic uremic syndrome, however, lab reports show atypical hemolytic uremic syndrome (low C3). Pain abdomen and loose stool with some signs of dehydration were initial presentations. Early initiation of renal replacement therapy and management of dehydration was done. Simple diarrhea can also manifest as acute kidney injury with the hemolytic uremic syndrome. Hence we should keep hemolytic uremic syndrome as the differential diagnosis of diarrhea. Irrespective of lab parameters, early management in line with the typical hemolytic uremic syndrome should be done for better outcomes. Keywords: anemia; case reports; dehydration; renal replacement therapy.

Catastrophic antiphospholipid syndrome accompanied by complement regulatory gene mutation.

BACKGROUND: Antiphospholipid syndrome (APS), particularly the catastrophic antiphospholipid syndrome (CAPS), is one of the rare causes of thrombotic microangiopathy (TMA). CAPS is the most severe form of APS, especially when accompanied by complement dysregulation, causes progressive microvascular thrombosis and failure in multiple organs. In this report, a case of CAPS with TMA accompanied by a genetic defect in the complement system is presented. CASE: A 13-year-old girl was admitted to the hospital with oliguric acute kidney injury, nephrotic range proteinuria, Coombs positive hemolysis, refractory thrombocytopenia, a low serum complement C3 level and anti-nuclear antibody (ANA) positivity. The kidney biopsy was consistent with TMA. She was first diagnosed with primary APS with clinical and pathological findings and double antibody positivity. As initial treatments, plasmapheresis (PE) was performed and eculizumab was also administered following pulsesteroid and intravenous immunoglobulin treatments. Her renal functions recovered and she was followed up with mycophenolate mofetil, hydroxychloroquine, low dose prednisolone and low molecular weight heparin treatments. The patient presented with severe chest pain, vomiting and acute deterioration of renal functions a few months after the diagnosis of TMA. A CAPS attack was considered due to radiological findings consistent with multiple organ thrombosis and intravenous cyclophosphamide (CYC) was given subsequent to PE. After pulse CYC and PE treatments, her renal functions recovered, she is still being followed for stage-3 chronic kidney disease. Complement factor H-related protein I gene deletion was detected in the genetic study. CONCLUSIONS: The clinical course of complement mediated CAPS tends to be worse. Complement system dysregulation should be investigated in all CAPS patients, and eculizumab treatment should be kept in mind if detected.

Sustained Response to Eculizumab in a Patient With COVID-19-Associated Acute Thrombotic Microangiopathy of the Allograft Kidney: A Case Report.

Acute thrombotic microangiopathy (TMA) developing in association with SARS-CoV-2 infection is a rare but recognized phenomenon in native kidneys. In the allograft kidney, a diagnosis of TMA has a broad etiologic differential, including antibody-mediated rejection and recurrent and de novo causes of TMA that affect the native kidney. Prior case reports have described plasma exchange or eculizumab use in patients with COVID-19-associated TMA. Herein, we describe the course of a kidney transplant patient with COVID-19-associated TMA with response to eculizumab that was sustained after medication withdrawal and review the literature on COVID-19-associated TMA of the allograft kidney.

Evaluation of Eculizumab Use in Renal Transplant Recipients.

Introduction: Eculizumab is a monoclonal antibody that binds to complement protein C5, inhibiting complement-mediated thrombotic microangiopathy. It is approved for several indications including atypical hemolytic uremic syndrome. Additionally, eculizumab is used off-label for antibody-mediated rejection and C3 glomerulopathy in renal transplant recipients. Due to limited data available, the purpose of this study was to describe the use of eculizumab treatment in renal transplant recipients. Design: This retrospective single-center study evaluated the safety and efficacy of eculizumab for on- and off-label indications in renal transplant recipients. Adult renal transplant recipients receiving at least 1 dose of eculizumab posttransplant between October 2018 and September 2021 were included. The primary outcome evaluated was graft failure in patients treated with eculizumab. Results: Forty-seven patients were included in analysis. The median age at eculizumab initiation was 51 years [IQR 38-60], with 55% being female. Indications for eculizumab included atypical hemolytic uremic syndrome/thrombotic microangiopathy (63.8%), antibody-mediated rejection (27.7%), C3 glomerulopathy (4.3%), and other (4.3%). Graft failure occurred in 10 patients (21.3%) with a median of 2.4 weeks [IQR 0.5-23.3] from transplant to graft failure. At last follow-up (median 56.1 weeks), 44 (93.6%) patients were alive. After eculizumab initiation, renal function improved at 1 week, 1 month, and last follow-up. Conclusion: Eculizumab treatment demonstrated a benefit on graft and patient survival compared to reported incidence in thrombotic microangiopathy and antibody-mediated rejection. Due to the small sample size and retrospective design, further research is warranted to confirm these results.