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 Use of Highly Individualized Complement Blockade Has Revolutionized Clinical Outcomes after Kidney Transplantation and Renal Epidemiology of Atypical Hemolytic Uremic Syndrome

2019 ◽  
Vol 30 (12) ◽  
pp. 2449-2463 ◽  
Author(s):  
Julien Zuber ◽  
Marie Frimat ◽  
Sophie Caillard ◽  
Nassim Kamar ◽  
Philippe Gatault ◽  
...  
Keyword(s):  
Cohort Study ◽  
Hemolytic Uremic Syndrome ◽  
Kidney Transplant ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Population Based ◽  
Adult Patients ◽  
Transplant Recipients ◽  
Risk Of Recurrence ◽  
Atypical Hus ◽  
Uremic Syndrome

BackgroundAtypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade–based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country.MethodsTo evaluate this strategy’s effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS (n=397) between 2007 and 2016.ResultsThe first study included 126 kidney transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients.ConclusionsResults from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial.

scholarly journals Clinical-Laboratory- Genetic Profile and Outcomes of Patients with Atypical Hemolytic Uremic Syndrome and Restrictive Use of Eculizumab: A Single Center Experience and a Brief Review

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3159-3159
Author(s):  
Fnu Amisha ◽  
Manojna Konda ◽  
Paras Malik ◽  
Arya Mariam Roy ◽  
Appalanaidu Sasapu
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Factor H ◽  
Genetic Profile ◽  
Complement Factor ◽  
Single Center ◽  
Inclusion Criteria ◽  
Atypical Hus ◽  
Uremic Syndrome

Abstract Background Atypical HUS (aHUS) is a rare thrombotic microangiopathy (TMA) caused by complement dysregulation. Eculizumab is a humanized monoclonal antibody targeting against complement factor C5. Ravulizumab, a longer acting C5 inhibitor developed through minimal, targeted modifications to eculizumab was recently approved for treatment of aHUS in 2019. Here we describe the clinical presentation, laboratory, genetic profile, treatment along with long-term sequelae of patients diagnosed with aHUS. The outcomes of restrictive use of eculizumab and the use of ravulizumab were also studied. Materials and Methods We conducted a single center retrospective cohort study, searching electronic medical records of patients diagnosed and treated for aHUS at University of Arkansas for Medical Sciences, from January 1, 2013 to January 31, 2021, after IRB approval. Inclusion criteria :1) Presence of microangiopathic hemolytic anemia (MAHA) with thrombocytopenia 2) ADAMTS13 activity > 10 % 3) Age > 18. Exclusion criteria: 1) Age < 18 years 2) TMA associated with hemolytic uremic syndrome, scleroderma renal crises, anti-phospholipid syndrome. Results Seventeen patients meeting the inclusion criteria were enrolled in the study. The mean age at diagnosis was 47.4 ± 17.9 years. Most of the patients were Caucasians (n=10, 58%) and females (n= 14, 82%). All the patients except one had acute kidney injury (AKI) at presentation (n=16, 94.1%), the most frequent extra-renal presentation was CNS involvement -seizures, confusion and altered mental status (n= 7, 41.2 %) followed by Gastrointestinal- non-bloody diarrhea, nausea and vomiting (n=5, 29.4 %) [Figure 1]. Lab investigations are described in [Table 1]. Complement genetic testing was done in 100% of study population. Factor H related genes 1/3 (CFHR1/3) and complement factor H (CFH) were the most commonly found pathogenic mutations [Table 2]. In this study, pregnancy and infection (n= 4, 23.5% each) were identified as the most common triggers [Figure 2]. For two of the patients, it was the first pregnancy and for the other two, it was their second and third pregnancies. They presented at the second, sixth, and sixteenth week postpartum respectively. Eleven (64.70%) patients developed chronic kidney disease (CKD) with six (35.29%) patients progressing to end stage renal disease (ESRD). Two (11.76 %) pregnant patients developed cardiomyopathy, two (11.76%) patients developed pulmonary complications (pneumonia and pulmonary hypertension) and three (17.64%) patients developed epilepsy. All the postpartum females in our study were able to breastfeed while on eculizumab with no long-term complications in the neonates. One patient had two subsequent deliveries with no ante, intra, or post-partum consequences or repeated triggers of aHUS. Fourteen patients (82.3%) received therapeutic plasma exchange, four (23.5%) patients received iv methyl prednisone (1mg/kg) and two (11.7%) patients received IVIg prior to initiating eculizumab. Over time, five (29.41%) patients opted to completely stop drug therapy and four patients (23.52%) chose to shift to ravulizumab because of the ease of treatment duration (every 8 weeks rather than every 2 weeks for eculizumab). All these nine patients remained in remission with stable hematologic and renal parameters on subsequent follow-ups [Table 3]. Three patients (17.6 % mortality) died in our study due to causes unrelated to aHUS. Conclusions: The clinical diagnosis of atypical HUS can be challenging especially with extra-renal manifestations. Females were four times more affected than males. PCMs were present in 11 patients. Early diagnosis and treatment with C5 inhibitors improves morbidity and mortality. The decision to discontinue or switch eculizumab to ravulizumab will likely decrease healthcare costs and improve patient compliance but should be based on disease severity. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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 First-line therapy in atypical hemolytic uremic syndrome: consideration on infants with a poor prognosis

2014 ◽  
Vol 40 (1) ◽  
Author(s):  
Nóra Szarvas ◽  
Ágnes Szilágyi ◽  
Velibor Tasic ◽  
Valbona Nushi-Stavileci ◽  
Aspazija Sofijanova ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Poor Prognosis ◽  
Atypical Hemolytic Uremic Syndrome ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Uremic Syndrome

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.

scholarly journals Atypical hemolytic uremic syndrome: A report of two cases

2016 ◽  
Vol 9 (1) ◽  
pp. 75
Author(s):  
Md. Habibur Rahman ◽  
Morsheda Akhter ◽  
Syed Symul Haque
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Kidney Injury ◽  
Course Of Illness ◽  
Atypical Hus ◽  
Excellent Outcome ◽  
Uremic Syndrome ◽  
Stage Renal Disease ◽  
End Stage ◽  
Insight Into

Hemolytic uremic syndrome (HUS) is one of the important cause of acute kidney injury in children. There is excellent outcome in patients with typical HUS but atypical HUS is associated with high mortality, risk of recurrence and may lead to end stage renal disease. We report two cases of 5 and 6 year old child having clinical &amp; laboratory characteristics of atypical HUS. These children had a fulminant course of illness with complications involving various systems. The report provides an insight into the etio pathogenesis, diagnoses and treatment of this condition.

Eculizumab as First-Line Therapy for Atypical Hemolytic Uremic Syndrome

PEDIATRICS ◽  
2014 ◽  
Vol 133 (6) ◽  
pp. e1759-e1763 ◽  
Author(s):  
M. Christmann ◽  
M. Hansen ◽  
C. Bergmann ◽  
D. Schwabe ◽  
J. Brand ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Uremic Syndrome
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