Successful Renal Transplantation in a Patient with Atypical Hemolytic Uremic Syndrome Carrying Mutations in Both Factor I and MCP

Kidney transplantation in patients with atypical hemolytic uremic syndrome (aHUS) carrying mutations in the soluble complement regulators factor H (CFH) or factor I (CFI) is associated with elevated risk of disease recurrence and almost certain graft loss. In contrast, recurrence is unusual in patients with mutations in the membrane-associated complement regulator membrane cofactor protein (MCP) (CD46). Therefore, a panel of experts recently recommended the combined liver–kidney transplantation to minimize aHUS recurrence in patients with mutations in CFH or CFI . There was, however, very limited information regarding transplantation in patients carrying mutations in both soluble and membrane-associated complement regulators to support a recommendation. Here, we report the case of an aHUS patient with a heterozygous mutation in both CFI and MCP who received an isolated kidney transplant expressing normal MCP levels. Critically, the patient suffered from a severe antibody-mediated rejection that was successfully treated with plasmapheresis and IvIgG. Most important, despite the complement activation in the allograft, there was no evidence of thrombotic microangiopathy, suggesting that the normal MCP levels in the grafted kidney were sufficient to prevent the aHUS recurrence. Our results suggest that isolated kidney transplantation may be a good first option for care in aHUS patients carrying CFI / MCP combined heterozygous mutations.     

Thrombotic Microangiopathy After Kidney Transplantation

Thrombotic microangiopathy (TMA) is a severe complication of kidney transplantation that often causes graft failure. TMA may occur de novo, often triggered by immunosuppressive drugs and acute antibody‐mediated rejection, or recur in patients with previous history of hemolytic uremic syndrome (HUS). Recurrent TMA is very rare in patients who had developed end‐stage renal failure following HUS caused by Shiga‐toxin producing E. scherichia coli, whereas disease recurrence is common in patients with atypical HUS (aHUS). The underlying genetic defect greatly impacts the risk of posttransplant recurrence in aHUS. Indeed recurrence is almost the rule in patients with mutations in genes encoding factor H or factor I, whereas patients with a mutation in membrane‐cofactor‐protein gene have a good transplant outcome. Prophylactic and therapeutic options for posttransplant TMA, including plasma therapy, combined kidney and liver transplantation and targeted complement inhibitors are discussed in this review.     

De novo thrombotic microangiopathy induced by cytomegalovirus infection leading to renal allograft loss

After kidney transplantation, thrombotic microangiopathy (TMA) can occur de novo or as recurrent disease. Risk factors for de novo posttransplant TMA include ischemia-reperfusion injury, immunosuppressive drugs, viral infections, acute humoral rejection, and complement gene abnormalities. Cytomegalovirus infection as a trigger for posttransplant TMA in kidney transplant recipients has only been reported in 7 cases, all of them between 4 weeks and 8 years after transplantation. We describe a new case of de novo TMA in association with cytomegalovirus infection 25 years after kidney transplantation.     

aHUS caused by complement dysregulation: new therapies on the horizon

Atypical hemolytic uremic syndrome (aHUS) is a heterogeneous disease that is caused by defective complement regulation in over 50% of cases. Mutations have been identified in genes encoding both complement regulators [complement factor H (CFH), complement factor I (CFI), complement factor H-related proteins (CFHR), and membrane cofactor protein (MCP)], as well as complement activators [complement factor B (CFB) and C3]. More recently, mutations have also been identified in thrombomodulin (THBD), an anticoagulant glycoprotein that plays a role in the inactivation of C3a and C5a. Inhibitory autoantibodies to CFH account for an additional 5–10% of cases and can occur in isolation or in association with mutations in CFH, CFI, CFHR 1, 3, 4, and MCP. Plasma therapies are considered the mainstay of therapy in aHUS secondary to defective complement regulation and may be administered as plasma infusions or plasma exchange. However, in certain cases, despite initiation of plasma therapy, renal function continues to deteriorate with progression to end-stage renal disease and renal transplantation. Recently, eculizumab, a humanized monoclonal antibody against C5, has been described as an effective therapeutic strategy in the management of refractory aHUS that has failed to respond to plasma therapy. Clinical trials are now underway to further evaluate the efficacy of eculizumab in the management of both plasma-sensitive and plasma-resistant aHUS.     

De novo thrombotic microangiopathy after kidney transplantation

Thrombotic microangiopathy (TMA) is a serious complication of transplantation that adversely affects kidney transplant recipient and allograft survival. Post-transplant TMA is usually classified into two categories: 1) recurrent TMA and 2) de novo TMA. Atypical hemolytic uremic syndrome (aHUS) resulting from dysregulation and over-activation of the alternate complement pathway is a rare disease but the most common diagnosis associated with recurrence in the allografts. De novo TMA, on the other hand, represents an overwhelming majority of the cases of post-transplant TMA and is a substantially more heterogeneous entity than recurrent aHUS. Here, we review the etio-pathogenesis, diagnosis and treatment options for de novo post-transplant TMA. It is usually in the setting of calcineurin inhibitor use, mammalian target of rapamycin inhibitor use, or antibody mediated rejection; recently genetic mutations in complement regulatory genes for Factor H and Factor I similar to those described in aHUS have been reported in up to a third of these patients. Systemic signs of TMA are frequently absent, and a renal allograft biopsy is often needed to establish the diagnosis. Although withdrawal of the offending agents is usually the first line of treatment and resolution of laboratory abnormalities has been documented with this approach in several case reports and case series, available retrospective data demonstrate lack of benefit in long-term graft outcomes. Co-stimulation blockage with belatacept provides an effective alternate immunosuppressive strategy for these patients. Anti-complement therapy with eculizumab is effective in some cases; further work is required to define which patients with TMA (with and without concomitant antibody-mediated rejection) would benefit from receiving this treatment, and what biomarkers can be used to identify them.     

De novo thrombotic microangiopathy in two kidney transplant recipients from the same deceased donor: A case series

Thrombotic microangiopathy (TMA) is a recognized and serious complication of renal transplantation. Atypical hemolytic uremic syndrome (aHUS), a subset of TMA, occurs in the setting of dysregulation of the alternative complement pathway and can cause disease in native kidneys as well as recurrence in allografts. De novo TMA represents a classification of TMA post-transplant in the absence of clinical or histopathological evidence of TMA or aHUS in the native kidney. De novo TMA is a more heterogeneous syndrome than aHUS and the pathogenesis and risk factors for de novo TMA are poorly understood. The association between calcineurin inhibitors (CNI) and de novo TMA is controversial. Anti-complement blockade therapy with eculizumab is effective in some cases, but more studies are needed to identify appropriate candidates for therapy. We present two cases of de novo TMA occurring immediately in recipients from the same deceased donor and provoking the question of whether deceased donor-related factors could represent risks for developing de novo TMA.     

Complement Activation During Liver Transplantation—Special Emphasis on Patients With Atypical Hemolytic Uremic Syndrome

Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy often caused by mutations in complement factor H (CFH), the main regulator of alternative complement pathway. Because CFH is produced mainly by the liver, combined liver–kidney transplantation is a reasonable option in treatment of patients with severe aHUS. We studied complement activation by monitoring activation markers during liver transplantation in two aHUS patients treated extensively with plasma exchange and nine other liver transplantation patients. After the reperfusion, a clear increase in all the activation markers except C4d was observed indicating that the activation occurs mainly through the alternative pathway. Concentration of SC5b‐9 was higher in the hepatic than the portal vein indicating complement activation in the graft. Preoperatively and early during the operation, the aHUS patients showed highest C3d concentrations but otherwise their activation markers were similar to the other patients. In the other patients, correlation was found between perioperative SC5b‐9 concentration and postoperative alanine aminotransferase and histological changes. This study explains why supply of normal CFH by extensive plasma exchange is beneficial before combined liver–kidney transplantation of aHUS patients. Also the results suggest that perioperative inhibition of the terminal complement cascade might be beneficial if enhanced complement activation is expected.     

Successful conversion to belatacept after thrombotic microangiopathy in kidney transplant patients

Thrombotic microangiopathy (TMA) is a severe complication of kidney transplantation. TMA may occur de novo or as recurrent disease post‐transplant. De novo disease is usually associated with immunosuppressive drugs or can be seen as a part of endothelial damage that accompanies antibody‐mediated rejection. Treatment for de novo TMA is limited to plasma exchange and change in immunosuppression. We report two cases of de novo TMA post‐transplant that were successfully treated by converting to belatacept for maintenance immunosuppression.     

Antibody Mediated Rejection Associated With Complement Factor H–Related Protein 3/1 Deficiency Successfully Treated With Eculizumab

Antibody mediated rejection (AMR) activates the classical complement pathway and can be detrimental to graft survival. AMR can be accompanied by thrombotic microangiopathy (TMA). Eculizumab, a monoclonal C5 antibody prevents induction of the terminal complement cascade (TCC) and has recently emerged as a therapeutic option for AMR. We present a highly sensitized 13‐year‐old female with end‐stage kidney disease secondary to spina bifida‐associated reflux nephropathy, who developed severe steroid‐, ATG‐ and plasmapheresis‐resistant AMR with TMA 1 week post second kidney transplant despite previous desensitization therapy with immunoglobulin infusions. Eculizumab rescue therapy resulted in a dramatic improvement in biochemical (C3; creatinine) and hematological (platelets) parameters within 6 days. The patient was proven to be deficient in complement Factor H‐related protein 3/1 (CFHR3/1), a plasma protein that regulates the complement cascade at the level of C5 conversion and has been involved in the pathogenesis of atypical hemolytic uremic syndrome caused by CFH autoantibodies (DEAP‐HUS). CFHR1 deficiency may have worsened the severe clinical progression of AMR and possibly contributed to the development of donor‐specific antibodies. Thus, screening for CFHR3/1 deficiency should be considered in patients with severe AMR associated with TMA.     

Tailored Eculizumab Therapy in the Management of Complement Factor H–Mediated Atypical Hemolytic Uremic Syndrome in an Adult Kidney Transplant Recipient: A Case Report

Atypical hemolytic uremic syndrome (aHUS) is characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney injury (AKI) which frequently progresses to end-stage renal disease (ESRD). In 50% of affected patients, mutations in complement regulatory proteins cause inappropriate complement activation with endothelial injury. Complement factor H (CFH) mutations cause 25% of aHUS cases; these patients have an 80% recurrence risk after kidney transplantation. Eculizumab, an anti-C5 antibody, is effective in limiting hemolysis episodes in patients with aHUS, but less is known about preventing recurrence after kidney transplantation. Herein we report the use of prophylactic eculizumab in an adult with aHUS who underwent kidney transplantation. A 31-year-old female presented with aHUS and progressive AKI associated with low complement 3 level leading to ESRD despite plasmapheresis and corticosteroids. She had a heterozygous nonsense mutation in CFH and reduced plasma CFH levels. She was given preoperative plasmapheresis and eculizumab and underwent living unrelated renal transplantation. Postoperatively, eculizumab was dosed to achieve low functional complement 5 levels and low soluble membrane attack complex levels and she has maintained excellent graft function without aHUS recurrence. We propose that eculizumab with titrated dosing should be used in CFH-mediated aHUS patients who are at a high risk of recurrence.     

Use of eculizumab and plasma exchange in successful combined liver–kidney transplantation in a case of atypical HUS associated with complement factor H mutation

Background

Atypical hemolytic uremic syndrome (aHUS) evolves into end-stage renal failure in nearly half of affected patients and is associated with defective regulation of the alternative complement pathway. Patients with a complement factor H (CFH) mutation have a 30–100% risk of graft loss due to aHUS recurrence or graft thrombosis. Since CFH is produced predominantly by the liver, combined liver–kidney transplant is a curative treatment option. One major unexpected risk includes liver failure secondary to uncontrolled complement activation. We report a successful combined liver–kidney transplantation with perioperative plasma exchange and use of the humanized anti-C5 monoclonal antibody eculizumab.

Case Diagnosis/Treatment

An 11-month-old female presented with oliguric renal failure after 3 weeks of flu-like symptoms in the absence of diarrhea. Following the identification of Escherichia coli 0157:H7 in her stool, she was discharged home on peritoneal dialysis with a diagnosis of Shiga toxin-associated HUS. Three months later, she developed severe anemia, thrombocytopenia, and neurological involvement. aHUS was diagnosed and confirmed, and genetic testing revealed a mutation in CFH SCR20. Once donor organs became available, she received preoperative plasma exchange followed by eculizumab infusion with intra-operative fresh frozen plasma prior to combined liver–kidney transplant. At 19 months post-transplant, she continues to have excellent allograft and liver function without signs of disease recurrence.

Conclusion

Perioperative use of eculizumab in conjunction with plasma exchange during simultaneous liver–kidney transplant can be used to inhibit terminal complement activity, thereby optimizing successful transplantation by reducing the risk of graft thrombosis.     

Eculizumab in the treatment of atypical hemolytic uremic syndrome in infants

A 28-day-old male newborn weighing 3.6 kg was given a diagnosis of atypical hemolytic-uremic syndrome, new-onset thrombotic microangiopathy (TMA; hemoglobin, 7.7 g/dL; schistocytes, 9%), thrombocytopenia (platelets, 49 × 10(3)/μL [49 × 10(9)/L]), and acute kidney failure (serum creatinine, 1.13 mg/dL [99.8 μmol/L], corresponding to estimated glomerular filtration rate [eGFR] of 15 mL/min/1.73 m(2) [0.25 mL/s/1.73 m(2)]). Repeated high-volume plasma infusions were ineffective. Plasma exchange was attempted, but not tolerated. The patient required mechanical ventilation and continuous renal replacement therapy. He developed multiple intestinal perforations and leg skin necrosis due to systemic TMA. A low C3 level (36 mg/dL) suggested complement activation. Eculizumab, 300 mg, was administered, and within 48 hours the patient recovered from acute kidney failure, with complete hematologic remission 2 weeks later. The infant, 14 months old at the time of writing, continues to receive eculizumab, 300 mg, every 3 weeks; he is free of disease activity and has a normal creatinine level of 0.2 mg/dL (17.68 μmol/L; corresponding to eGFR of 110 mL/min/1.73 m(2) [1.83 mL/s/1.73 m(2)]), but mild proteinuria (urinary protein-creatine ratio, 1 mg/g). Results of additional studies, including probing for cobalamin anomalies and measuring levels of ADAMTS13, complement factor H (CFH), factor I (CFI), and membrane cofactor protein (MCP), were unremarkable. Antibodies to CFH were undetectable, and mutation testing of the genes for CFH, CFI, and MCP gave negative results. Treatment with eculizumab was life saving, and with continued treatment, the patient showed sustained freedom from clinical TMA complications.     

Eculizumab for the treatment of de novo thrombotic microangiopathy post simultaneous pancreas-kidney transplantation--a case report

A 34-year-old female recipient of a simultaneous pancreas-kidney transplant presented 7 days posttransplant with acute renal allograft dysfunction, thrombocytopenia, and microangiopathic hemolytic anemia. Renal biopsy revealed acute antibody-mediated rejection (AMR) and acute thrombotic microangiopathy (TMA). Clinical and laboratory manifestations, which had only partly responded to treatment with daily plasma exchange and intravenous immunoglobulin, resolved rapidly and completely to eculizumab (Soliris, Alexion Pharmaceuticals, Inc., Cheshire, Conn), a complement factor C5 antibody. De novo posttransplant TMA is a rare and serious complication that can lead to graft loss in up to one third of cases. This is the first report of successful treatment of de novo TMA with eculizumab, which has previously shown benefit in recurrent atypical hemolytic uremic syndrome as well as in refractory acute AMR. Targeted complement inhibition offers the promise of a safe and effective therapeutic strategy in de novo TMA, especially in light of recent evidence suggesting that genetic mutations in complement regulatory proteins may predispose transplant recipients to this serious disease.     

Thrombotic microangiopathy after kidney transplantation

Two forms of post-transplant thrombotic microangiopathy (TMA) may be recognized: recurrent TMA and de novo TMA. Recurrent TMA may occur in patients who developed a nondiarrhoeal form of haemolytic uraemic syndrome (HUS) being particularly frequent in patients with autosomal recessive or dominant HUS. The recurrence is almost the rule in patients with mutation in complement factor H gene. Most patients eventually lose the graft. Treatment with plasma infusions or plasmapheresis is often disappointing, but few cases may be rescued. Intravenous immunoglobulins and rituximab have also been successful in anedoctic cases. De novo TMA is rarer. A number of factors including viral infection may be responsible of de novo TMA, but in most cases TMA is triggered by calcineurin inhibitors or mTOR inhibitors. The clinical presentation of de novo TMA may be variable with some patients showing clinical and laboratory features of HUS while others showing only a progressive renal failure. The prognosis is less severe than with recurrent TMA. Complete withdrawal of the offending drug may lead to improvement in many cases. The addition of plasma exchange may result in graft salvage in about 80% of cases.     

A Favorable 3-Year Outcome of Kidney Transplantation in Atypical Hemolytic Uremic Syndrome Associated With a Factor H Mutation: Case Report

Complement factor H (CFH)-associated hemolytic uremic syndrome (HUS) is a genetic form of atypical HUS characterized by deficient CFH levels or activity, which cause a disorder of the regulation of the alternative pathway, leading to uncontrolled complement activation. This genetic disorder, which frequently leads to end-stage renal failure, often recurs in kidney transplants, resulting in the poorest graft outcomes among all atypical HUS forms, due to a mutation in genes encoding complement components and regulatory proteins. Herein we have report our experience with a 40-year-old woman, suffering from a clearly defined sporadic form of genetic atypical HUS, consisting of a heterozygous missense mutation in factor H gene. She underwent cadaveric kidney transplantation. At the moment of surgery she displayed positive hemolysis indices and C3 consumption. A calcineurin inhibitor (CNI)-free immunosuppressive regimen was based on sirolimus, mycophenolic acid and steroids after basiliximab induction. An early and intense prophylactic course of plasma exchange (PE), and fresh frozen plasma (40 mL/kg) was prescribed, starting before surgery and continuing daily for the first week. The frequency of PE slowly reduced over the following 2 weeks. After that, just plasma infusion at the same dose was performed once a week until 12 weeks after transplantation. There was prompt graft function and in third week there were no signs of hemolysis or of C3 consumption. More than 3 years after transplantation, the graft is still functioning well and there was no recurrence. In our opinion, this case indicates that, although evidence is lacking, avoidance of CNI and intensive prophylactic plasma therapy are essential to achieve good results in this peculiar type of kidney transplantation. Nevertheless, controlled, prospective studies are necessary to establish the actual role of these two therapeutic procedures in renal transplantation of patients with CFH-associated HUS.     

Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome

Mutations in factor H (CFH), factor I (IF), and membrane cofactor protein (MCP) genes have been described as risk factors for atypical hemolytic uremic syndrome (aHUS). This study analyzed the impact of complement mutations on the outcome of 46 children with aHUS. A total of 52% of patients had mutations in one or two of known susceptibility factors (22, 13, and 15% of patients with CFH, IF, or MCP mutations, respectively; 2% with CFH+IF mutations). Age <3 mo at onset seems to be characteristic of CFH and IF mutation-associated aHUS. The most severe prognosis was in the CFH mutation group, 60% of whom reached ESRD or died within <1 yr. Only 30% of CFH mutations were localized in SCR20. MCP mutation-associated HUS has a relapsing course, but none of the children reached ESRD at 1 yr. Half of patients with IF mutation had a rapid evolution to ESRD, and half recovered. Plasmatherapy seemed to have a beneficial effect in one third of patients from all groups except for the MCP mutation group. Only eight (33%) of 24 kidney transplantations that were performed in 15 patients were successful. Graft failures were due to early graft thrombosis (50%) or HUS recurrence. In conclusion, outcome of HUS in patients with CFH mutation is catastrophic, and posttransplantation outcome is poor in all groups except for the MCP mutation group. New therapies are urgently needed, and further research should elucidate the unexplained HUS group.     

Recurrence of hemolytic uremic syndrome after renal transplantation

Non-Shiga toxin-associated hemolytic uremic syndrome (non-Stx-HUS) is a rare disease. The clinical outcome is often unfavorable: 50% of patients progress to end-stage renal failure. Several mutations in complement regulatory genes predispose to non-Stx-HUS. Transplantation outcomes are poor among patients with either mutation in the genes encoding complement H or I factors, with 80% graft loss due to HUS recurrence. In contrast, patients with mutation in the gene encoding MCP have no disease relapse after transplantation. There are no treatment guidelines for non-Stx-HUS recurrence. Herein we have presented 8 patients with non-Stx-HUS recurrence after transplantation during the last 10 years in the South of France. HUS recurrence, which occurred early after transplantation in all but 1 patient, was treated by plasma exchange (PE) with substitution by fresh frozen plasma (FFP). Three patients still treated with long-term plasma therapy have no recurrence at 15, 19, or 24 months. An international registry would help to define new guidelines.     

Successful 7-Year Eculizumab Treatment of Plasmapheresis-Resistant Recurrent Atypical Hemolytic-Uremic Syndrome due to Complement Factor H Hybrid Gene: A Case Report

Atypical hemolytic-uremic syndrome (aHUS) is an extremely rare disease, and up to 70% of the patients have a genetic mutation in the encoding components of complement activation or anti-complement factor H autoantibodies. The risk of recurrence after kidney transplantation is 10% to 80%. Eculizumab, a monoclonal antibody that binds complement protein C5, has shown to be highly effective in patients with aHUS; however, there are only few reports on the efficacy and safety of long-term eculizumab treatment in children with recurrent aHUS. Only 3 case reports regard treatment in patients with complement factor H (CFH/CFHR1/CFHR3) hybrid gene. This report presents the efficacy and safety of long-term eculizumab treatment in a child with recurrent aHUS who has been successfully treated with eculizumab for more than 7 years. The patient presented as a 9-year-old with aHUS due to CFH/CFHR1/CFHR3 hybrid gene and received deceased donor kidney transplantation. After the transplantation, he experienced recurrence of aHUS 2 months later. Daily plasma exchanges were ineffective in the transplanted kidney; the patient became anuric and hemodialysis was needed. Eculizumab was started as therapy and led to complete remission of aHUS including restoration of diuresis. Eculizumab has been given as therapy for 7 years. The young patient is in a sustained remission without any adverse events. This patient is only the sixth patient reported with recurrent aHUS due to CFH/CFHR1/CFHR3 hybrid gene and is the patient with the longest remission of recurrent aHUS ever published.     

Complement and the atypical hemolytic uremic syndrome in children

Over the past decade, atypical hemolytic uremic syndrome (aHUS) has been demonstrated to be a disorder of the regulation of the complement alternative pathway. Among approximately 200 children with the disease, reported in the literature, 50% had mutations of the complement regulatory proteins factor H, membrane cofactor protein (MCP) or factor I. Mutations in factor B and C3 have also been reported recently. In addition, 10% of children have factor H dysfunction due to anti-factor H antibodies. Early age at onset appears as characteristic of factor H and factor I mutated patients, while MCP-associated HUS is not observed before age 1 year. Low C3 level may occur in patients with factor H and factor I mutation, while C3 level is generally normal in MCP-mutated patients. Normal plasma factor H and factor I levels do not preclude the presence of a mutation in these genes. The worst prognosis is for factor H-mutated patients, as 60% die or reach end-stage renal disease (ESRD) within the first year after onset of the disease. Patients with mutations in MCP have a relapsing course, but no patient has ever reached ESRD in the first year of the disease. Half of the patients with factor I mutations have a rapid evolution to ESRD, but half recover. Early intensive plasmatherapy appears to have a beneficial effect, except in MCP-mutated patients. There is a high risk of graft loss for HUS recurrence or thrombosis in all groups except the MCP-mutated group. Recent success of liver–kidney transplantation combined with plasmatherapy opens this option for patients with mutations of factors synthesized in the liver. New therapies such as factor H concentrate or complement inhibitors offer hope for the future.     

Belatacept as Maintenance Immunosuppression for Postrenal Transplant de novo Drug-Induced Thrombotic Microangiopathy

De novo posttransplant thrombotic microangiopathy (TMA) is a complication of solid organ transplantation, which remains difficult to treat. In many cases, immunosuppressants and particularly calcineurin inhibitors, trigger TMA. Although withdrawing the offending drug may lead to resolution of TMA, graft and patient outcomes are poor. Specific treatments, including plasma exchange, have not gained widespread acceptance in those with fulminant disease and new approaches to the condition are urgently needed.
We report a case of posttransplant de novo TMA presenting serially in association with ciclosporin, tacrolimus and sirolimus in a young recipient of a living donor kidney transplant. We describe a patient treated with belatacept, a novel CTLA4 Ig fusion protein, as ongoing maintenance immunosuppression to allow avoidance of conventional agents once associated with TMA. We report excellent early graft outcome, with no adverse events using this strategy. We suggest that belatacept may have a role in this traditionally difficult-to-treat group of patients.