Expert Statements on the Standard of Care in Critically Ill Adult Patients With Atypical Hemolytic 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.

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Erratum to “Rondeau E, Scully M, Ariceta G, Barbour T, Cataland S, Heyne N, Miyakawa Y, Ortiz S, Swenson E, Vallee M, Yoon S-S, Kavanagh D, Haller H; on behalf of the 311 Study Group. The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment” Kidney Int. 2020;97:1287–1296

Kidney International ◽

10.1016/j.kint.2020.11.001 ◽

2020 ◽

Vol 98 (6) ◽

pp. 1621

Author(s):

Eric Rondeau ◽

Marie Scully ◽

Gema Ariceta ◽

Tom Barbour ◽

Spero Cataland ◽

...

Keyword(s):

Hemolytic Uremic Syndrome ◽

Atypical Hemolytic Uremic Syndrome ◽

Adult Patients ◽

Study Group ◽

Complement Inhibitor ◽

Uremic Syndrome ◽

Long Acting ◽

Inhibitor Treatment

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P0082CHARACTERISTICS OF ADULT PATIENTS WITH ATYPICAL HEMOLYTIC UREMIC SYNDROME IN RUSSIA

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p0082 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Kseniya Demyanova ◽

Natalia Kozlovskaya ◽

Yuia Korotchaeva

Keyword(s):

Hemolytic Uremic Syndrome ◽

Renal Dysfunction ◽

Adult Population ◽

Atypical Hemolytic Uremic Syndrome ◽

Kidney Damage ◽

Adult Patients ◽

Acute Episode ◽

Plasma Therapy ◽

Gastrointestinal Lesions ◽

Uremic Syndrome

Abstract Background and Aims Atypical hemolytic uremic syndrome (aHUS) is complement mediated thrombotic microangiopathy (TMA), caused by genetic abnormalities in the complement gene cluster. Information about the course of aHUS in the adult population in Russia is not enough accumulated. This study presents the characteristics of Russian adult patients (pts) with aHUS. Aim To assess the characteristics of adult pts with aHUS in Russia. Method statistical analysis of retrospective and prospective data The study included 243 pts with acute TMA (microangiopathic hemolytic anemia, thrombocytopenia, decreased haptoglobin and / or blood schizocytosis, kidney damage) from different regions of Russia. All patients were tested for ADAMTS-13 activity, and there were no accidents of TTP in our study. Cases of acute TMA associated with pregnancy and childbirth (n=134), systemic diseases (n=10), anticancer drugs treatment (n=1) and sepsis (n=13) were excluded. 85 pts with diagnosis of aHUS were selected for further analysis. Results Characteristics of pts are presented in table 1. The average age at the time of acute episode was 32.4 years, the disease was equally common among men and women. Relapsing course was rare (n=11, 13%), the maximum number of relapses – 5. In the debut, 67.8% of pts had signs of kidney damage, in 21% - gastrointestinal tract, 4.8% - CNS, 4.8% - pulmonary thromboembolism, 1.6% - visual impairment. During the acute episode, extrarenal manifestations were detected in 70% of pts, while in 38 cases (44.7%), multiple organ failure (MOF) developed with simultaneous damage from 3 to 7 organs. The most commonly observed symptoms of gastrointestinal lesions (n = 39, 45%), CNS (n = 32, 37%), heart (n = 18, 21%), less often - the organ of vision (n = 10, 12%). Kidney damage was characterized by the development of AKI in 70%, in the rest - urinary syndrome, arterial hypertension, the initial signs of renal dysfunction in various combinations. A morphological examination of kidney was performed in 40 pts (kidney biopsy - 35, autopsy - 5): acute TMA was detected in 28 pts (70%), chronic TMA - in 7 (17.5%), a combination of acute and chronic TMA - in 2 (5%), a combination of IgA-nephropathy and TMA - in 1 case (2.5%) and in 2 patients a membrane-proliferative glomerulonephritis pattern with TMA. Genetic analysis was performed in 19 pts (22%), in 7 of which (37%) identified gene variants associated with the development of aHUS (C3 in 3 pts, CFHR5 in 2 pts, CFH in 2, in 1 case - MCP and in 1-DGKE). In addition, variants of genes of the complement system with an unclear clinical value were found in all pts (n = 19). 72% of pts (n = 61) needed renal replacement therapy, almost all pts received plasma therapy (83%) and anticoagulants (85%). Only 13 pts (15%) received complement-blocking therapy with eculizumab. In the outcome of the acute episode in 12 cases (14%) renal function fully recovered, in 20 pts (23%) signs of renal dysfunction persisted (CKD 2–4 stages), 53 pts (62.3%) reached ESRD, 10 pts died (12%). Conclusion The features of aHUS in our cohort were: 1. Severe course with the development of MOF in 45% of cases 2. High frequency of ESRD in the outcome of aHUS (62.3%) 3. The incidence of genetic mutations (37%) is comparable to foreign cohorts

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The long-acting C5 inhibitor, Ravulizumab, is effective and safe in adult patients with atypical hemolytic uremic syndrome naïve to complement inhibitor treatment

Kidney International ◽

10.1016/j.kint.2020.01.035 ◽

2020 ◽

Vol 97 (6) ◽

pp. 1287-1296 ◽

Cited By ~ 14

Author(s):

Eric Rondeau ◽

Marie Scully ◽

Gema Ariceta ◽

Tom Barbour ◽

Spero Cataland ◽

...

Keyword(s):

Hemolytic Uremic Syndrome ◽

Atypical Hemolytic Uremic Syndrome ◽

Adult Patients ◽

Complement Inhibitor ◽

Uremic Syndrome ◽

Long Acting ◽

Inhibitor Treatment

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Efficacy and safety of eculizumab in adult patients with atypical hemolytic uremic syndrome: A single center experience from Turkey

Transfusion and Apheresis Science ◽

10.1016/j.transci.2016.09.017 ◽

2016 ◽

Vol 55 (3) ◽

pp. 357-362 ◽

Cited By ~ 6

Author(s):

Fusun Gediz ◽

Bahriye Kadriye Payzin ◽

Sertac Ecemis ◽

Naile Güler ◽

Asu Fergun Yilmaz ◽

...

Keyword(s):

Hemolytic Uremic Syndrome ◽

Atypical Hemolytic Uremic Syndrome ◽

Adult Patients ◽

Efficacy And Safety ◽

Single Center ◽

Single Center Experience ◽

Uremic Syndrome

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The experience of using the Russian biosimilar of the original drug eculizumab for the treatment of patients with atypical hemolytic-uremic syndrome

Terapevticheskii arkhiv ◽

10.26442/00403660.2020.06.000649 ◽

2020 ◽

Vol 92 (6) ◽

pp. 76-80

Author(s):

Yulia V. Lavrishcheva ◽

Alexander A. Yakovenko ◽

Dmitrii A. Kudlai

Keyword(s):

Hemolytic Uremic Syndrome ◽

Thrombotic Microangiopathy ◽

High Efficiency ◽

Systemic Disease ◽

Atypical Hemolytic Uremic Syndrome ◽

Adult Patients ◽

Alternative Complement Pathway ◽

Complement Pathway ◽

Alternative Complement ◽

Uremic Syndrome

Atypical hemolytic-uremic syndrome (aHUS) is a chronic systemic disease of a genetic nature, which is based on uncontrolled activation of the alternative complement pathway, leading to generalized thrombosis in the vessels of the microvasculature (complement-mediated thrombotic microangiopathy). To date, therapy with eculizumab is the most effective and pathogenetically substantiated method of treating patients with ASH. Using the example of three clinical cases of patients with a verified diagnosis of aHUS, the high efficiency and safety of the worlds first bioanalogue of eculizumab in the treatment of adult patients with aHUS (complement-mediated thrombotic microangiopathy) was demonstrated.

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The Global aHUS Registry: Characteristics of 826 Patients with Atypical Hemolytic Uremic Syndrome

Blood ◽

10.1182/blood.v126.23.4640.4640 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4640-4640

Author(s):

Christoph Licht ◽

Gianluigi Ardissino ◽

Gema Ariceta ◽

David J. Cohen ◽

Christoph Gasteyger ◽

...

Keyword(s):

Hemolytic Uremic Syndrome ◽

Board Of Directors ◽

Research Funding ◽

Atypical Hemolytic Uremic Syndrome ◽

Age Groups ◽

Adult Patients ◽

Employment Equity ◽

Advisory Committees ◽

Uremic Syndrome ◽

Equity Ownership

Abstract Background: Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, life-threatening disease predominantly caused by chronic, uncontrolled complement activation that leads to thrombotic microangiopathy and renal and other end-organ damage. The aHUS Registry, established in April 2012, is an observational, noninterventional, multicenter, global initiative to collect information on patient outcomes regardless of treatment approach. It facilitates availability of follow-up data for eculizumab. Methods: Patients with clinical diagnoses of aHUS (irrespective of identified complement abnormality or treatment) are eligible. Demographic, medical/disease history, and treatment outcomes data are collected at enrollment and prospectively thereafter. Results: By June 30, 2015, 826 patients enrolled (Table). Overall, 54.7% of patients, including 45.1% of pediatric and 62.7% of adult patients, were female. Patients were most commonly enrolled after their first TMA event. Thrombosis occurred more frequently in adult than pediatric patients. Nonrenal conditions, including gastrointestinal, cardiovascular, central nervous system, and pulmonary, were common in both age groups and occurred in 11.0%‒20.3% overall. Eculizumab was administered to 57.3% of patients, of whom 87.3% were treated prior to enrollment. Conclusions: Registry baseline characteristics demonstrate differences between pediatric and adult patients with aHUS, notably frequencies of thrombosis. Nonrenal conditions are frequent in both age groups. Ongoing and future analyses will further enhance understanding of aHUS history and progression. Additional clinical sites are encouraged to enroll patients to facilitate knowledge acquisition and optimization of patient care and quality of life. Disclosures Licht: Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Achillon: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Ardissino:Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Ariceta:Alexion Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees. Cohen:Astellas: Consultancy; Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Merck: Consultancy; Genentech: Research Funding. 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, Equity Ownership. Kupelian:Alexion Pharmaceuticals: Employment, Equity Ownership. Schaefer:Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees. Vande Walle:Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Frémeaux-Bacchi:Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

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