Use of eculizumab in atypical uremic hemolytic syndrome in childhood: case report (original) (raw)
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Pediatric Drugs, 2016
Introduction Studies relating to first-line, early, and longterm eculizumab treatment and outcomes in children with atypical hemolytic uremic syndrome (aHUS) are scarce and unclear. The aim of this case-series study was to evaluate the outcomes of first-line, early, and long-term eculizumab treatment in our aHUS patients. Materials and Methods We reviewed the data from four pediatric patients with aHUS who were treated with eculizumab. In three of them, eculizumab was used as a firstline therapy, and the follow-up period was C2 years in three patients. Results Plasma exchange could not be performed in any patient. Plasma infusions were used only in Patient 1 (a 14-month-old boy) for 8 days without any response. Therefore, eculizumab was started on day 11 after admission. Patient 2 (a 16-month-old boy), Patient 3 (an 11-yearold girl), and Patient 4 (a 32-month-old girl) were treated with eculizumab as a first-line therapy, which was started 2-4 days after admission. The dosage of eculizumab was adjusted according to body weight. The hematologic parameters (the time frames were 3-17 days) and C 3 (the time frames were 10-17 days) returned to normal in all patients after receipt of eculizumab. Although Patient 1 developed stage III chronic kidney disease, complete renal recovery occurred in Patients 2 and 4. Patient 3 also had reflux nephropathy with bilateral grade III vesicoureteral reflux and renal scars. Her creatinine clearance returned to the baseline value after receiving eculizumab. No complications related to eculizumab were observed in any patient during the follow-up period. Conclusion Eculizumab can be successfully used as a firstline therapy in pediatric aHUS patients. We observed that the early initiation of eculizumab was associated with the complete recovery of renal function. Key Points Early and first-line initiation of eculizumab may be more effective for complete renal recovery in children with aHUS. Ideally, treatment should begin within the first 4 days of presentation.
Kidney International, 2016
A typical hemolytic uremic syndrome (aHUS) is a progressive life-threatening thrombotic microangiopathy (TMA) associated with dysregulation of the complement alternative pathway. 1-3 Complement gene mutations (e.g., complement factor H [CFH], membrane cofactor protein [MCP], complement factor I [CFI], complement factor B [CFB], complement protein 3 [C3]), or factor H autoantibodies are identified in 50% to 60% of patients with aHUS. 4-6 Abnormalities in genes encoding thrombomodulin, plasminogen, and diacylglycerol kinase ε (DGKE) 7-9 occur in a small number of patients. Evidence of a genetic abnormality is not required for diagnosis. 4,10-13 Although onset may occur at any age, 40% of patients develop aHUS by 18 years of age. 1,2,5 Clinical manifestations in children generally include anemia, thrombocytopenia, and acute kidney injury, 5 but peripheral gangrene, 14 arterial stenoses, 15 dilated cardiomyopathy, cardiorespiratory arrest, 16 and neurologic, 5,17 pulmonary, 11 and gastrointestinal complications 17 have been reported. Historically, aHUS was managed with plasma exchange/plasma infusion (PE/PI) and was associated with high morbidity and mortality rates, 1-3,5,18 with children having higher mortality than adults. 5 PE/PI may induce stabilization of hematologic parameters (but generally not significant renal function improvement), 19 is associated with complications, and impairs quality of life. 19,20 The availability of eculizumab (Soliris, Alexion Pharmaceuticals, Inc., Cheshire, CT, USA) 21,22an anti-C5 monoclonal antibody and the first and only currently approved therapy for adult and pediatric patients-has profoundly changed aHUS management. 13,23 The efficacy and safety of
Rapid Resolution of Atypical Hemolytic Uremic Syndrome by Eculizumab Treatment
Childhood Kidney Diseases
Atypical hemolytic uremic syndrome (aHUS) is an extremely rare and life-threatening disorder. Typical HUS is often caused by Shiga toxin-positive Escherichia coli, while aHUS is caused by dysregulation of the alternative pathway of the complement system in association with genetic abnormalities or development of autoantibodies. Eculizumab, a humanized anti-complement 5 monoclonal antibody, is recommended for the treatment of aHUS, but its long-term safety and efficacy in pediatric patients remain under review. In this paper, we report a pediatric case of aHUS with anti-complement factor H autoantibodies, who was treated successfully with eculizumab.
Pediatric Nephrology, 2011
Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy associated with defective regulation of the alternative complement pathway. The prognosis for patients with aHUS is poor, and plasma exchange represents the first-line therapy. Eculizumab is a humanized monoclonal anti-C5 antibody that prevents the activation of the terminal complement pathway. Here, we report the case of a 9-year-old girl with frequent relapsing aHUS due to heterozygous factor H mutation who was initially treated with plasma exchange three times per week with 150% plasma exchange volume. This treatment frequently caused allergic reactions and school absences. Because any reduction in the frequency of plasma exchange immediately induced relapses of the aHUS, treatment with eculizumab, 600 mg every 2 weeks, was started and plasma exchange completely stopped. On this drug regimen the patient showed no evidence of disease activity during a period of more than 24 months. Renal function improved, proteinuria disappeared, the number of antihypertensive medications could be decreased, and the quality of life increased substantially. The inhibition of the terminal complement pathway by eculizumab was also confirmed by renal biopsy, which showed the absence of thrombotic microangiopathy 2 months after the initiation of eculizumab therapy. This case illustrates the long-term favorable outcome of aHUS with eculizumab treatment.
Neonatal onset atypical hemolytic uremic syndrome successfully treated with eculizumab
Pediatric Nephrology, 2013
Background Atypical hemolytic uremic syndrome (aHUS) is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Neonatal cases are extremely uncommon. Plasma therapy is the first choice therapy in patients with aHUS based on the belief of an underlying complement dysregulation. Alternatively, eculizumab, which targets complement 5, is used to block complement activation. Case-diagnosis/treatment Sudden onset macroscopic hematuria, hypertension, and bruises over the entire body were noted in a 5 day-old newborn. Investigations revealed hemolytic anemia, thrombocytopenia, renal impairment, and a low serum C3, leading to the diagnosis of aHUS. Fresh frozen plasma (FFP) infusions and peritoneal dialysis for acute kidney injury were initiated. This approach yielded full renal and hematological remission. The patient was discharged with FFP infusions, but subsequently developed three life-threatening disease recurrences at 1, 3, and 6 months of age. The last relapse presented with uncontrolled hypertension and impaired renal function while the patient was receiving FFP infusions. After the first dose of eculizumab, his renal and hematological parameters returned to normal and his blood pressure normalized. Genetic screening of the CFH gene revealed a novel homozygous p. Tyr1177Cys mutation. Conclusion Eculizumab can be considered as an alternative to plasma therapy in the treatment of specific patients with aHUS, even in infants.
A systematic review on the efficacy and safety of eculizumab for atypical hemolytic uremic syndrome
Journal of Renal Injury Prevention, 2018
Context: To date, several studies have been done regarding the treatment of atypical hemolytic uremic syndrome (aHUS) which discussed eculizumab as a potential treatment for this syndrome. However, the safety and efficacy of eculizumab were not fully assessed. This study aims to do a systematic review about the efficacy and safety of eculizumab in treatment of aHUS. Evidence Acquisitions: An electronic literature search was conducted to identify appropriate studies. We included all randomized trials and observational studies about using eculizumab in aHUS. Two independent reviewers extracted data from the articles according to the selection criteria. Results: Eligible studies were included in this systematic review. The literature search and reference mining yielded 571 potential relevant articles. We removed 173 articles because of duplication. We also excluded 245 articles after reviewing the titles and abstracts, and removed 61 studies because the topics were not relevant to the ...
Acta Scientific Medical Sciences, 2020
Atypical hemolytic uremic syndrome is a rare form of thrombotic microangiopathies resulting from various genetic mutations of the complement factors. Thrombotic microangiopathies include Thrombotic thrombocytopenic purpura, primary HUS further divided into typical HUS or Shiga-toxin related HUS, atypical HUS and secondary forms of HUS. The most common clinical features of the Hemolytic Uremic Syndrome are: kidney failure, thrombocytopenia resulting in hemorrhagic phenomena and also intravascular hemolytic anemia. Most commonly HUS is a diagnosis made from excluding all other plausible causes. HUS predominantly affects pediatric ages.
Romanian Journal of Internal Medicine, 2021
Introduction: To evaluate the effect of therapeutic plasma exchange(TPE) and eculizumab on hematological and renal survival in atypical hemolytic uremic syndrome(aHUS). Additionally, to examine the reliability of discontinuation of eculizumab treatment. Methods: This was an observational and retrospective study of 18 patients diagnosed with aHUS. Results: The median age of the study population was 30(22-66) years. Four of 18 patients achieved hematological remission with the TPE alone. However, one patient in the died after three sessions of TPE. Eculizumab was used in 13 patients and no death was observed. One year after treatment, improved kidney function was observed in 2 of 3(66%) patients for TPE and 5 of 9(56%) patients for Eculizumab. We discontinued eculizumab treatment in 9 patients. One of the patients who had a C3 gene mutation experienced disease relapse after Eculizumab discontinuation. None of the patients who had drug associated aHUS, developed disease relapse after E...
Continued Eculizumab Therapy for Persistent Atypical Hemolytic Uremic Syndrome
The Open Urology & Nephrology Journal, 2013
Atypical hemolytic uremic syndrome (atypical HUS) is characterized by endothelial injury and microvascular thrombosis resulting in microangiopathic hemolytic anemia, thrombocytopenia, and ischemic injury to organs, especially the kidney. Activation of complements is involved in the pathogenesis of atypical HUS. Eculizumab, a neutralizing monoclonal antibody directed against complement C5, has shown salutary effects in patients with atypical HUS. In this report, we present a 23-year-old man with atypical HUSwho was treated with eculizumab. During the first four weeks of treatment, eculizumab failed to achieve a remission. Microangiopathic hemolytic anemia and thrombocytopenia persisted, while renal function deteriorated necessitating initiation of hemodialysis. Continuation of eculizumab therapy, however, led to marked improvement in hemolytic anemia, thrombocytopenia, and renal function. After 10 weeks of eculizumab therapy, hemodialysis was discontinued. At 5-month follow-up, serum creatinine was 1.1 mg/dL with continued eculizumab therapy every other week. In addition, platelet count was normal, while there was no evidence of hemolysis. We conclude that in patients with persistent atypical HUS continued treatment with eculizumab can be helpful in achieving remission.