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.

SP005PREVENTIVE PLASMA THERAPY FOR PREVENTION OF ATYPICAL HEMOLYTIC UREMIC SYNDROME RELAPSE FOLLOWING KIDNEY TRANSPLANTATION

2019 ◽  
Vol 34 (Supplement_1) ◽  
Author(s):  
Christof Aigner ◽  
Georg A Böhmig ◽  
Farsad Eskandary ◽  
Harald Herkner ◽  
Zoltán Prohászka ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Plasma Therapy ◽  
Uremic Syndrome

Influence of genotype on clinical characteristics of atypical hemolytic uremic syndrome (aHUS) with pediatric and adult onset

2009 ◽  
Vol 46 (14) ◽  
pp. 2839
Author(s):  
V. Fremeaux-Bacchi ◽  
F. Fakhouri ◽  
A. Garnier ◽  
F. Bienaime ◽  
A.L. Sellier-Leclerc ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Clinical Characteristics ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Adult Onset ◽  
Uremic Syndrome

P0082CHARACTERISTICS OF ADULT PATIENTS WITH ATYPICAL HEMOLYTIC UREMIC SYNDROME IN RUSSIA

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

scholarly journals Differential Impact of Complement Mutations on Clinical Characteristics in Atypical Hemolytic Uremic Syndrome

2007 ◽  
Vol 18 (8) ◽  
pp. 2392-2400 ◽  
Author(s):  
Anne-Laure Sellier-Leclerc ◽  
Veronique Fremeaux-Bacchi ◽  
Marie-Agnès Dragon-Durey ◽  
Marie-Alice Macher ◽  
Patrick Niaudet ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Clinical Characteristics ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Differential Impact ◽  
Uremic Syndrome

A complicated case of atypical hemolytic uremic syndrome with frequent relapses under eculizumab

2015 ◽  
Vol 30 (6) ◽  
pp. 1039-1042 ◽  
Author(s):  
Gesa Schalk ◽  
Michael Kirschfink ◽  
Cyrill Wehling ◽  
Sara Gastoldi ◽  
Carsten Bergmann ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Complicated Case ◽  
Frequent Relapses ◽  
Uremic Syndrome

scholarly journals Pregnancy-triggered atypical hemolytic uremic syndrome (aHUS): a Global aHUS Registry analysis

2021 ◽  
Author(s):  
Fadi Fakhouri ◽  
Marie Scully ◽  
Gianluigi Ardissino ◽  
Imad Al-Dakkak ◽  
Benjamin Miller ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Clinical Characteristics ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Factor H ◽  
Complement Factor ◽  
Childbearing Age ◽  
History Of ◽  
Uremic Syndrome ◽  
Stage Renal Disease ◽  
End Stage

Abstract Background Atypical hemolytic uremic syndrome (aHUS) is a rare disease in which uncontrolled terminal complement activation leads to systemic thrombotic microangiopathy (TMA). Pregnancy can trigger aHUS and, without complement inhibition, many women with pregnancy-triggered aHUS (p-aHUS) progress to end-stage renal disease (ESRD) with a high risk of morbidity. Owing to relatively small patient numbers, published characterizations of p-aHUS have been limited, thus the Global aHUS Registry (NCT01522183, April 2012) provides a unique opportunity to analyze data from a large single cohort of women with p-aHUS. Methods The demographics and clinical characteristics of women with p-aHUS (n = 51) were compared with those of women of childbearing age with aHUS and no identified trigger (non-p-aHUS, n = 397). Outcome evaluations, including renal survival according to time to ESRD, were compared for patients with and without eculizumab treatment (a complement C5 inhibitor) in both aHUS groups. Results Baseline demographics and clinical characteristics were broadly similar in both groups. The proportion of women with p-aHUS and non-p-aHUS with pathogenic variant(s) in complement genes and/or anti-complement factor H antibodies was similar (45% and 43%, respectively), as was the proportion with a family history of aHUS (12% and 13%, respectively). Eculizumab treatment led to significantly improved renal outcomes in women with aHUS, regardless of whether aHUS was triggered by pregnancy or not: adjusted hazard ratio for time to ESRD was 0.06 (p = 0.006) in the p-aHUS group and 0.20 (p < 0.0001) in the non-p-aHUS group. Conclusion Findings from this study support the characterization of p-aHUS as a complement-mediated TMA. Graphic abstract

scholarly journals Phenotypic manifestation of homozygous partial deletion of the chromosome 1 segment spanning CFHR3 region

2020 ◽  
Vol 22 (3) ◽  
pp. 569-576
Author(s):  
I. A. Tuzankina ◽  
M. A. Bolkov ◽  
N. S. Zhuravleva ◽  
Yu. O. Vaseneva ◽  
Kh. Shinvari ◽  
...  
Keyword(s):  
Renal Failure ◽  
Hemolytic Uremic Syndrome ◽  
Clinical Case ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Clinical Manifestations ◽  
Factor H ◽  
Complement Factor H ◽  
Chromosome 1 ◽  
Complement Factor ◽  
Uremic Syndrome

This article presents two clinical cases of patients with a homozygous deletion of segment of chromosome 1, which covers regions of genes associated with complement factor H, in particular CFHR3. Patients underwent in-depth clinical studies, heredity assessment, laboratory, instrumental and genetic diagnostics. The first clinical case describes a clinical case with deleted chromosome 1 segment in a 9-year-old girl who was diagnosed with atypical hemolytic-uremic syndrome. This is a complement-dependent disease that affects both adults and children. It is known that a defect in any proteins included in the alternative complement activation pathway can lead to atypical hemolytic-uremic syndrome. However, this syndrome is most often caused by defects in chromosome 1 region, including gene sequences associated with complement factor H – CFHR1 and CFHR3. Modern treatment of atypical hemolytic uremic syndrome involves targeted pathogenetic treatment, therefore, the genetic diagnosis seems to be a necessary step for differential diagnosis and confirmation. The patient had fairly typical clinical symptoms, including signs of thrombotic microangiopathy, thrombocytopenia, hemolytic anemia and increasing renal failure. It is also known that her mother had congenital hydronephrosis, and the pregnancy proceeded against a background of ureaplasma, mycoplasma, cytomegalovirus infection, chronic pyelonephritis, and preeclampsia.The second clinical case of a deleted chromosome 1 region, involving the CFHR3 gene, is a description of the disease in a boy of 8 years old, while the disease manifested with alopecia at the age of 4. Intermittent alopecia was the main symptom, while there were no signs of renal failure, thrombocytopenic purpura, and other symptoms characteristic of atypical hemolytic-uremic syndrome. The boy also revealed some congenital defects of the urinary system: bladder diverticulum, unilateral ureterohydronephrosis, and bilateral dilatation of the pyelocaliceal system. The detected genetic defect is usually associated with atypical hemolytic uremic syndrome. However, the phenotype, i.e., clinical manifestations, determined a completely different diagnosis – primary immunodeficiency, a group of complement defects, and a deficiency of complement factor H-related protein. After analyzing the given clinical cases, we can conclude that clinical manifestations may vary significantly in carriers of same gene mutations. This suggests that there are additional factors (genetic or environmental) that can influence the formation of various phenotypic manifestations of this pathology.

scholarly journals Atypical hemolytic uremic syndrome: what is it, how is it diagnosed, and how is it treated?

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 617-625 ◽  
Author(s):  
Carla M. Nester ◽  
Christie P. Thomas
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Thrombotic Microangiopathy ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Complete Characterization ◽  
Clinical Syndrome ◽  
Plasma Therapy ◽  
Alternate Pathway ◽  
Uremic Syndrome ◽  
Time Of Presentation

Abstract Atypical hemolytic uremic syndrome (aHUS) is a rare syndrome of hemolysis, thrombocytopenia, and renal insufficiency. Genetic mutations in the alternate pathway of complement are well recognized as the cause in more than 60% of patients affected by this thrombotic microangiopathy. The identification of aHUS as a disease of the alternate pathway of complement enables directed therapeutic intervention both in the acute and chronic setting and may include one or all of the following: plasma therapy, complement blockade, and liver transplantation. Because aHUS shares many of the presenting characteristics of the other thrombotic microangiopathies, and confirmatory genetic results are not available at the time of presentation, the diagnosis relies heavily on the recognition of a clinical syndrome consistent with the diagnosis in the absence of signs of an alternate cause of thrombotic microangiopathy. Limited understanding of the epidemiology, genetics, and clinical features of aHUS has the potential to delay diagnosis and treatment. To advance our understanding, a more complete characterization of the unique phenotypical features of aHUS is needed. Further studies to identify additional genetic loci for aHUS and more robust biomarkers of both active and quiescent disease are required. Advances in these areas will undoubtedly improve the care of patients with aHUS.

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