scholarly journals Discontinuation of Peritoneal Dialysis after Late Initiation of Eculizumab in a Case of Familial Atypical Hemolytic-Uremic Syndrome: A Case Report

2017 ◽  
Vol 7 (1) ◽  
pp. 18-25 ◽  
Author(s):  
Rafael Alonso Valente ◽  
Giannina Elena García Rodríguez ◽  
Yanina García Marcote ◽  
Manuel Fidalgo Díaz ◽  
Vanesa Becerra Mosquera ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Hemolytic Uremic Syndrome ◽  
Regulatory Gene ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Poor Response ◽  
Organ Damage ◽  
Laboratory Findings ◽  
Late Initiation ◽  
Late Treatment ◽  
Uremic Syndrome

Background: Atypical hemolytic-uremic syndrome is caused by a thrombotic microangiopathy and manifests itself with hemolytic anemia, thrombocytopenia, and organ ischemia. Its etiology is a mutation affecting the genes encoding for proteins of the complement system. Early treatment with eculizumab (8.6 months from the moment of presentation), a humanized monoclonal antibody against complement, is shown to be effective in controlling symptoms and reversing organ damage. We present a patient with a mutation not previously described in the literature. Late treatment with eculizumab resulted in a good therapeutic response, eliminating the need for peritoneal dialysis. Case Presentation: A 34-year-old woman showed symptoms and laboratory findings consistent with atypical hemolytic-uremic syndrome. Genetic analysis revealed an unusual mutation of the complement regulatory gene not seen previously. Due to unavailability of eculizumab at the time of presentation, conventional treatment was started with poor response. Late initiation of eculizumab resulted in discontinuation of peritoneal dialysis and yielded a good and sustained clinical response. Conclusions: This case shows that eculizumab treatment for patients with atypical hemolytic-uremic syndrome, even when initiated many months after beginning on dialysis, might offer substantial benefits and improve the patients’ quality of life.

scholarly journals MP518DISCONTINUATION OF PERITONEAL DIALYSIS (PD) AFTER LATE INITIATION OF ECULIZUMAB IN A PATIENT WITH FAMILIAL ATYPICAL HEMOLYTIC UREMIC SYNDROME (aHUS): A CASE REPORT

2016 ◽  
Vol 31 (suppl_1) ◽  
pp. i512-i512
Author(s):  
Rafael Alonso Valente ◽  
Suleyka Puello Martínez ◽  
Marta Duran Beloso ◽  
Iyad Abuward Abusharkh ◽  
Teresa Cordal Martínez ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Case Report ◽  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Late Initiation ◽  
Uremic Syndrome

scholarly journals Atypical hemolytic uremic syndrome secondary to lupus nephritis, responsive to eculizumab

2016 ◽  
Vol 8 (3) ◽  
Author(s):  
Alexander G. Raufi ◽  
Shruti Scott ◽  
Omar Darwish ◽  
Kevin Harley ◽  
Kanwarpal Kahlon ◽  
...  
Keyword(s):  
Lupus Nephritis ◽  
Hemolytic Uremic Syndrome ◽  
Lupus Erythematosus ◽  
Multidisciplinary Approach ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Organ Damage ◽  
Atypical Hus ◽  
First Line Therapy ◽  
Autoimmune Attack ◽  
Uremic Syndrome

Among the spectrum of disease manifestations associated with systemic lupus erythematosus, lupus nephritis is particularly concerning due to the potential for renal failure. This autoimmune attack may not, however, be limited to the kidney and is increasingly being recognized as a trigger for atypical Hemolytic Uremic Syndrome (aHUS). Atypical HUS falls under the spectrum of the thrombotic microangiopathies (TMAs) – a group of disorders characterized by microangiopathic hemolytic anemia, thrombocytopenia, and end organ damage. Although plasma exchange is considered first-line therapy for thrombotic thrombocytopenic purpura – a TMA classically associated with autoimmune depletion of ADAMTS-13 – aHUS demonstrates less reliable responsiveness to this modality. Instead, use of the late complement inhibitor Eculizumab has emerged as an effective modality for the management of such patients. Diagnosis of aHUS, however, is largely clinically based, relying heavily upon a multidisciplinary approach. Herein we present the case of a patient with atypical HUS successfully treated with Eculizumab in the setting of Class IV-G (A) lupus nephritis and hypocomplementemia.

scholarly journals Clinical characteristics and genetic backgrounds of Japanese patients with atypical hemolytic uremic syndrome

2018 ◽  
Vol 22 (5) ◽  
pp. 1088-1099 ◽  
Author(s):  
Madoka Fujisawa ◽  
Hideki Kato ◽  
Yoko Yoshida ◽  
Tomoko Usui ◽  
Munenori Takata ◽  
...  
Keyword(s):  
Mortality Rate ◽  
Hemolytic Uremic Syndrome ◽  
Clinical Characteristics ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Clinical Manifestations ◽  
Total Mortality ◽  
Plasma Therapy ◽  
Laboratory Findings ◽  
Frequent Relapses ◽  
Uremic Syndrome

Abstract Background Atypical hemolytic uremic syndrome (aHUS) is caused by complement overactivation, and its presentation and prognosis differ according to the underlying molecular defects. The aim of this study was to characterize the genetic backgrounds of aHUS patients in Japan and to elucidate the associations between their genetic backgrounds, clinical findings, and outcomes. Methods We conducted a nationwide epidemiological survey of clinically diagnosed aHUS patients and examined 118 patients enrolled from 1998 to 2016 in Japan. We screened variants of seven genes related to complement and coagulation, as well as positivity for anti-CFH antibodies, and assessed clinical manifestations, laboratory findings, and clinical course. Results The most frequent genetic abnormalities were in C3 (31%) and the frequency of CFH variants was relatively low (10%) compared to Western countries. The predominant variant in this cohort was C3 p.I1157T (23%), which was related to favorable outcomes despite frequent relapses. A total of 72% of patients received plasma therapy, while 42% were treated with eculizumab. The prognosis of Japanese aHUS patients was relatively favorable, with a total mortality rate of 5.4% and a renal mortality rate of 15%. Conclusions The common occurrence of genotype C3, especially the p.I1157T variant was the characteristic of the genetic backgrounds of Japanese aHUS patients that differed from those of Caucasian patients. In addition, the favorable prognosis of patients with the unique C3 p.I1157T variant indicates that understanding the clinical characteristics of individual gene alterations is important for predicting prognosis and determining therapeutic strategies in aHUS.

scholarly journals Baseline Demographics and Characteristics of 466 Patients with Atypical Hemolytic Uremic Syndrome in the Global aHUS Registry

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4204-4204
Author(s):  
Christoph Licht ◽  
Gianluigi Ardissino ◽  
Gema Ariceta ◽  
David Cohen ◽  
Christoph Gasteyger ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Board Of Directors ◽  
Research Funding ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Organ Damage ◽  
Advisory Committees ◽  
Life Threatening ◽  
History Of ◽  
Uremic Syndrome ◽  
The Uk

Abstract Introduction:Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, life-threatening disease of chronic, uncontrolled complement activation leading to thrombotic microangiopathy, renal, and other end-organ damage. Started in April 2012, the aHUS Registry is an observational, non-interventional, multicenter, global registry designed to collect information on patients (pts) with aHUS. By making follow-up data on the aHUS indication for eculizumab (ECU) available, the Registry fulfills postmarketing regulatory requirements while also highlighting the need for and benefit of a sponsor/academia partnership. An independent Scientific Advisory Board ensures data are made accessible for publication. Herein, we report baseline demographics and clinical characteristics of pts enrolled in the aHUS Registry. Methods:Pts of all ages with a clinical diagnosis of aHUS (irrespective of treatment) are eligible for enrollment into the Registry. An identified complement abnormality is not required. Demographic, medical and disease history, treatment, and efficacy and safety outcomes data are collected at Registry enrollment and prospectively thereafter. Results:By July 1, 2014, 466 pts (from Australia, Austria, Belgium, Canada, France, Germany, Israel, Italy, Russia, Spain, Sweden, Switzerland, the UK, and USA) were enrolled in the aHUS Registry. Of these, 261 (56.0%) were treated with ECU and 286 (61.4%) were ≥18 years of age. Family history of aHUS, prior kidney grafts, dialysis, plasma exchange/plasma infusion (PE/PI), and renal impairment were assessed at baseline in ECU- and non–ECU-treated pts (Table). Mean time from aHUS diagnosis to ECU initiation was 2.5 years. Sixty-five pts (24.9%) discontinued ECU; of these, 8 (12.3%) restarted. Conclusions:Since the public disclosure of data from the last aHUS Registry update, pt enrollment has continued to increase. Ongoing and future analyses will further clinicians’ understanding of the history and progression of aHUS. Additional clinical sites are encouraged to enroll pts into the aHUS Registry to facilitate knowledge acquisition and optimization of pt care and quality of life. Disclosures Licht: Achillon Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Ardissino:Alexion Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ariceta:Alexion Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cohen:Alexion Pharmaceuticals: Consultancy. Gasteyger:Alexion Pharma International Sàrl: Employment, Equity Ownership. Greenbaum:Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ogawa:Alexion Pharmaceuticals: Employment. Schaefer:Alexion Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Vande Walle:Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Fremeaux-Bacchi:Alexion Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; CLS Behring: Honoraria.

scholarly journals Long-Term Management of Atypical Hemolytic Uremic Syndrome after Non-Renal Solid Organ Transplantation with Eculizumab

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3466-3466
Author(s):  
Kruti Sheth ◽  
Raffaele Girlanda ◽  
Catherine Broome
Keyword(s):  
Serum Creatinine ◽  
Hemolytic Uremic Syndrome ◽  
Clinical Laboratory ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Organ Damage ◽  
Solid Organ ◽  
Uremic Syndrome ◽  
Term Management

Abstract Thrombotic microangiopathy (TMA) defined as microangiopathic hemolytic anemia, thrombocytopenia and end organ damage has been described in the post transplant (PT) setting after solid organ and hematopoietic stem cell transplants (HSCT). The true incidence among non-renal solid organ transplant (NRSOT) recipients is unknown. Reported rates range from 2-30% (Verbiest 2014). Despite standard interventions such as plasma exchange and/or reduction in calcineurin inhibitor (CNI) therapy, 3-month mortality rates remain as high as 40% in NRSOT patients who develop PT-TMA. In HSCT and renal transplant recipients, it has been demonstrated that complement plays a central role in the development of PT-TMA, analogous to atypical hemolytic uremic syndrome (aHUS) (Zuber 2011; Jodele 2013). Based on similar clinical manifestations and etiology, PT-TMA should be defined by the same laboratory criteria as aHUS and treated with eculizumab (ECU), a monoclonal antibody directed against C5 (Sheth, ASH 2014). We previously reported the successful use of ECU for the acute treatment of PT-aHUS in NRSOT patients (Broome, ASH 2013). We report the long-term data on this cohort of patients here. Between January 2012-Novemeber 2013, 10 patients (8 small bowel, 2 liver), were diagnosed with PT-aHUS utilizing established clinical criteria for de novo aHUS. All patients were on CNI therapy at the time of diagnosis. The median time from transplant to TMA diagnosis was 10.5 months (range 1-53 months). All patients received standard aHUS dosing of ECU (with meningococcal vaccinations and antibiotic prophylaxis). By 1 month of ECU therapy, all patients demonstrated normalization of hematologic parameters and 4 of the 5 patients on hemodialysis (HD) at the time of ECU initiation were able to discontinue HD. At a median follow-up of 24 months, 7 patients remain on therapy (range 18-43 months). One patient had ECU discontinued at 3 months by the transplant team. Two patients have died: one at 3 months of therapy due to sepsis/multi-organ failure and the other at 6 months of therapy due to PT lymphoproliferative disorder/graft failure (GF). The 7 patients remaining on ECU had no clinical/laboratory evidence of recurrence of PT-aHUS (Table 1). No new HD has been initiated in the follow-up period. All remained on CNI therapy (tacrolimus) for prevention of transplant rejection. One patient on ECU therapy developed GF. No serious infections have been reported to date. ECU is an effective therapy for the long-term management of PT-aHUS in NRSOT recipients. Prompt initiation of ECU appears to result in an increased likelihood of reversal of end organ damage related to TMA. The 2 patients with GF (240 days, 572 days) and the 1 patient who remained on HD (180 days) had extended intervals from laboratory evidence of PT-aHUS to initiation of ECU, suggesting prolonged complement mediated TMA may contribute to irreversible organ damage. With early ECU therapy, 86% of patients have healthy graft function and 80% of patients were able to discontinue HD. Despite ongoing CNI therapy, renal function, as measured by serum creatinine, has continued to improve demonstrating the benefit of long-term ECU therapy. The observed decline in haptoglobin, an acute phase reactant, at 12 and 18 months suggests a decrease in systemic inflammation with constant complement regulation mediated by ECU, illustrating the systemic nature of PT-aHUS. All patients remained on both CNI and ECU without infectious complications, demonstrating the ability to successfully administer more than one immune mediator in NRSOT patients with PT-aHUS concurrently. The mortality rate in our cohort of NRSOT recipients with PT-aHUS is 20%, significantly less than prior reports of up to 70%. We propose treatment with ECU at the earliest clinical/laboratory signs of aHUS to prevent the morbidity and mortality associated with PT-aHUS in NRSOT patients. Future studies should prospectively evaluate ECU therapy in PT-aHUS to better define the risks and benefits of this therapy in NRSOT patients. Table 1. Median Laboratory Values Post ECU At diagnosis 1 month 3 months 6 months 12 months 18 months Platelets k/uL 86 151 p=.01 175 p=.04 177 p=.01 191 p=.04 168 p=.07 Serum Creatinine mg/dL 2.26 1.54 p=.03 1.42 p=.05 1.28 p=.04 0.97 p=.13 1.18 p=.13 LDH units/L 369 302 p=.23 206 p=.17 186 p=.17 235 p=.23 158 p=.21 Haptoglobin mg/dL <8 115 p=.00 154 p=.01 136 p=.02 67 p=.03 90 p=.04 Disclosures Broome: Alexion Pharmaceuticals: Consultancy, Honoraria, Research Funding.

Atypical hemolytic uremic syndrome: from diagnosis to treatment

2015 ◽  
Vol 53 (11) ◽  
Author(s):  
Massimo Franchini
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Shiga Toxin ◽  
Thrombotic Microangiopathy ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Rare Condition ◽  
Organ Damage ◽  
Thrombocytopenic Purpura ◽  
Haemolytic Uremic Syndrome ◽  
Uremic Syndrome

AbstractThrombotic microangiopathy (TMA) is a relatively rare condition but a medical urgency requiring immediate intervention to avoid irreversible organ damage or death. Symptoms on presentation include microangiopathic haemolytic anaemia, thrombocytopenia and organ damage. The most frequent direct causes of TMA are thrombotic thrombocytopenic purpura (TTP) and haemolytic uremic syndrome (HUS). The most common form of HUS is related to Shiga toxin producing

scholarly journals Atypical hemolytic uremic syndrome: a brief review

2017 ◽  
Vol 9 (2) ◽  
Author(s):  
Kuixing Zhang ◽  
Yuxin Lu ◽  
Kevin T. Harley ◽  
Minh-Ha Tran
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Regulatory Gene ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Kidney Injury ◽  
Regulatory Mechanisms ◽  
Complement Inhibitor ◽  
Loss Of Function ◽  
Microangiopathic Hemolytic Anemia ◽  
Uremic Syndrome ◽  
Glomerular Capillaries

Atypical hemolytic uremic syndrome (aHUS) is a disease characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury. The histopathologic lesions of aHUS include thrombotic microangiopathy involving the glomerular capillaries and thrombosis involving arterioles or interlobar arteries. Extra-renal manifestations occur in up to 20% of patients. The majority of aHUS is caused by complement system defects impairing ordinary regulatory mechanisms. Activating events therefore lead to unbridled, ongoing complement activity producing widespread endothelial injury. Pathologic mutations include those resulting in loss-of-function in a complement regulatory gene (<em>CFH, CFI, CD46</em> or <em>THBD</em>) or gain-of-function in an effector gene (<em>CFB</em> or <em>C3</em>). Treatment with the late complement inhibitor, eculizumab – a monoclonal antibody directed against C5 – is effective.

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