De novo systemic atypical hemolytic uremic syndrome in an ABO-incompatible living kidney transplant recipient with a novel pathogenic CFHR1 gene mutation successfully treated with eculizumab: a case report.

De novo systemic atypical hemolytic uremic syndrome (aHUS) post-kidney transplant is an uncommon entity associated with unfavorable outcome. We herein report a case of systemic and fulminant de novo aHUS accompanied by heart and respiratory failure in a 48-year-old male receiving ABO-incompatible living-related kidney transplant who was successfully treated with the anti-C5 monoclonal antibody eculizumab with complete recovery of allograft function. Genetic testing demonstrated a novel pathogenic heterozygous complement factor H-related 1 gene mutation in both the donor and the recipient. Our study highlights the high risks of post-transplant aHUS due to the complement gene mutations in both donor and recipient in living-related transplantation. Early intervention with eculizumab may be effective for reversing systemic aHUS in kidney transplant recipients.

Li D ，Wang W ，Chen R ，Wen J ，Zhang M ... -  《-》

Eculizumab and Belatacept for De Novo Atypical Hemolytic Uremic Syndrome Associated With CFHR3-CFHR1 Deletion in a Kidney Transplant Recipient: A Case Report.

Atypical hemolytic uremic syndrome (aHUS) is associated with significant morbidity and mortality and occurs due to genetic or acquired abnormalities that result in the dysregulation of the alternative complement pathway. We report a case of post-living kidney transplantation de novo aHUS in a setting of heterozygous deletion in the complement factor H-related protein (CFHR)3-CFHR1 gene. The aHUS episode was possibly triggered by antibody-mediated rejection or tacrolimus. The patient responded well to eculizumab and substituting belatacept for tacrolimus. Her serum creatinine level was stable at 1.5 mg/dL after 2.5 years of follow-up. This case highlights the success of using a strategy that combines eculizumab and belatacept, as an alternative to calcineurin inhibitors, in treating aHUS in a patient with heterozygous deletion in the CFHR3-CFHR1 gene.

Dedhia P ，Govil A ，Mogilishetty G ，Alloway RR ，Woodle ES ，Abu Jawdeh BG ... -  《-》

Early relapse of atypical hemolytic uremic syndrome following ABO-incompatible living-related pediatric kidney re-transplant successfully treated with eculizumab.

A 3-year-old girl with clinical features of atypical HUS (complement Factor I mutation inherited from an asymptomatic mother and Factor H autoantibodies) was treated with plasma exchange, progressed to kidney failure (KF) aged 4 years, and received an en bloc kidney DCD transplant aged 8 years with primary graft non-function necessitating transplant nephrectomy at the time of transplantation. She subsequently underwent re-transplantation from her father. This is a retrospective study of electronic patient records and medical notes. A 9-year-old girl received an ABO-incompatible (ABOi) living-related kidney transplant from her father with recipient and donor blood groups of O and A, respectively, with baseline recipient anti-A titers 1:128 reducing to 1:4 at the time of transplant with B lymphocyte depletion with rituximab and four sessions of immunoadsorption. Six hours post-transplant, she had recurrence of aHUS and received the first dose of eculizumab. She continues on monthly home eculizumab infusions with stable kidney allograft function and negative anti-A titers 7 years post-kidney transplantation. This is the first report of a pediatric high-risk ABOi living-related kidney transplantation in whom early relapse of aHUS was successfully treated with eculizumab with good long-term patient and allograft outcome.

Stojanovic J ，Adamusiak A ，Waters A ，Sebire NJ ，Kessaris N ，Mamode N ，Marks SD ... -  《-》

Living Donor Kidney Transplantation in Atypical Hemolytic Uremic Syndrome: A Case Series.

The development of complement inhibitors has greatly improved the outcome of patients with atypical hemolytic uremic syndrome (aHUS), making kidney transplantation a more feasible option. Although prophylactic eculizumab therapy may prevent recurrent disease after transplantation, its necessity for all transplant recipients is debated. A case series. Patients with aHUS who underwent living donor kidney transplantation after 2011 at 2 university centers, prospectively followed up with a protocol of eculizumab therapy limited to only recipients with documented posttransplantation recurrent thrombotic microangiopathy. In addition, the protocol emphasized lower target level tacrolimus and aggressive treatment of high blood pressure. Recurrence of aHUS, kidney function, acute kidney injury. We describe 12 female and 5 male patients with a mean age of 47 years. 5 patients had lost a previous transplant due to aHUS recurrence. 16 patients carried a pathogenic or likely pathogenic variant in genes encoding complement factor H, C3, or membrane cofactor protein, giving a high risk for aHUS recurrence. Median follow-up after transplantation was 25 (range, 7-68) months. One patient had aHUS recurrence 68 days after transplantation, which was successfully treated with eculizumab. 3 patients were treated for rejection and 2 patients developed BK nephropathy. At the end of follow-up, median serum creatinine concentration was 106 (range, 67-175) μmol/L and proteinuria was negligible. Small series and short duration of follow-up. Living donor kidney transplantation in aHUS without prophylactic eculizumab treatment appears feasible.

Duineveld C ，Verhave JC ，Berger SP ，van de Kar NCAJ ，Wetzels JFM ... -  《-》

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.

Vondrák K ，Seeman T 《-》