scholarly journals Acute Progression of Adult-Onset Atypical Hemolytic-Uremic Syndrome due to CFH Mutation: A Case Report

2013 ◽  
Vol 2013 ◽  
pp. 1-4
Author(s):  
Bartlomiej Posnik ◽  
Dorota Sikorska ◽  
Krzysztof Hoppe ◽  
Krzysztof Schwermer ◽  
Krzysztof Pawlaczyk ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Late Onset ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Genetic Mutation ◽  
Current Data ◽  
Factor H ◽  
Rapid Progression ◽  
Uremic Syndrome ◽  
Stage Renal Disease ◽  
End Stage

Atypical hemolytic-uremic syndrome (aHUS), unlike typical HUS, is not due to bacteria but rather to an idiopathic or genetic cause that promotes dysregulation of the alternative complement pathway. It leads to hemolytic anemia, thrombocytopenia, and renal impairment. Although aHUS secondary to a genetic mutation is relatively rare, when occurring due to a mutation in Factor H (CFH), it usually presents with younger onset and has a more severe course, which in the majority ends with end-stage renal failure. Paradoxically to most available data, our case features acute aHUS due to a CFH mutation with late onset (38-year-old) and rapid progression to end-stage renal disease. Due to current data indicating a high risk of graft failure in such patients, the diagnosis of aHUS secondary to a genetic cause has disqualified our patient from a living (family) donor renal transplantation and left her with no other option but to begin permanent renal replacement therapy.

scholarly journals A prevalent C3 mutation in aHUS patients causes a direct C3 convertase gain of function

Blood ◽  
2012 ◽  
Vol 119 (18) ◽  
pp. 4182-4191 ◽  
Author(s):  
Lubka T. Roumenina ◽  
Marie Frimat ◽  
Elizabeth C. Miller ◽  
Francois Provot ◽  
Marie-Agnes Dragon-Durey ◽  
...  
Keyword(s):  
At Risk ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Factor H ◽  
Complement C3 ◽  
Rapid Progression ◽  
Incomplete Penetrance ◽  
Inflammatory Stimuli ◽  
Uremic Syndrome ◽  
Stage Renal Disease ◽  
End Stage

Abstract Atypical hemolytic uremic syndrome (aHUS) is a rare renal thrombotic microangiopathy commonly associated with rare genetic variants in complement system genes, unique to each patient/family. Here, we report 14 sporadic aHUS patients carrying the same mutation, R139W, in the complement C3 gene. The clinical presentation was with a rapid progression to end-stage renal disease (6 of 14) and an unusually high frequency of cardiac (8 of 14) and/or neurologic (5 of 14) events. Although resting glomerular endothelial cells (GEnCs) remained unaffected by R139W-C3 sera, the incubation of those sera with GEnC preactivated with pro-inflammatory stimuli led to increased C3 deposition, C5a release, and procoagulant tissue-factor expression. This functional consequence of R139W-C3 resulted from the formation of a hyperactive C3 convertase. Mutant C3 showed an increased affinity for factor B and a reduced binding to membrane cofactor protein (MCP; CD46), but a normal regulation by factor H (FH). In addition, the frequency of at-risk FH and MCP haplotypes was significantly higher in the R139W-aHUS patients, compared with normal donors or to healthy carriers. These genetic background differences could explain the R139W-aHUS incomplete penetrance. These results demonstrate that this C3 mutation, especially when associated with an at-risk FH and/or MCP haplotypes, becomes pathogenic following an inflammatory endothelium-damaging event.

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 Preemptive Use of Eculizumab for Living-Donor Kidney Transplantation in a Child with Atypical Hemolytic Uremic Syndrome

2016 ◽  
Vol 30 (1&2) ◽  
pp. 22 ◽  
Author(s):  
Oleh Akchurin ◽  
Samriti Dogra ◽  
Frederick Kaskel ◽  
Dominique Jan ◽  
Stuart Greenstein ◽  
...  
Keyword(s):  
Kidney Transplantation ◽  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Factor H ◽  
Complement Factor ◽  
Pediatric Kidney Transplantation ◽  
Uremic Syndrome ◽  
Few Data ◽  
Stage Renal Disease ◽  
End Stage

Eculizumab is an anti-complement C5 monoclonal antibody that has recently been reported as an effective therapy for atypical hemolytic uremic syndrome. However, few data are available on the preemptive use of this medication in pediatric kidney transplantation. This report describes a successful preemptive use of eculizumab in combination with living unrelated kidney transplanta- tion in a 10-year-old child with end-stage renal disease secondary to atypical hemolytic uremic syndrome who has a complement factor H mutation that has not been previously reported. Further observations and clinical trials are required to address the challenges and areas of uncertainty related to preemptive eculizumab therapy for kidney transplantation in children and adults with atypical hemolytic uremic syndrome. 

scholarly journals Atypical Hemolytic Uremic Syndrome Successfully Treated with Eculizumab

2020 ◽  
Vol 95 (2) ◽  
pp. 124-128
Author(s):  
Jung Hyun Kim ◽  
Won Kyung Han ◽  
Yu Bum Choi ◽  
Hyung Jong Kim ◽  
Jisu Oh ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
End Stage Renal Disease ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Delayed Diagnosis ◽  
Membrane Attack Complex ◽  
Acute Renal Injury ◽  
Humanized Monoclonal Antibody ◽  
Uremic Syndrome ◽  
Stage Renal Disease ◽  
End Stage

Atypical hemolytic uremic syndrome (aHUS) is a rare syndrome characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute renal injury, which results from uncontrolled complement activation. Delayed diagnosis and treatment of aHUS may result in end-stage renal disease (ESRD) and an associated dependence on dialysis. In extreme cases, it may cause death due to multi-organ failure. Eculizumab, a humanized monoclonal antibody against C5, inhibits the formation of the terminal membrane attack complex and is used to treat aHUS. Here, we report a 46-year-old male patient who suffered from aHUS relapse, despite prior treatment with repeated plasma exchange and hemodialysis. Eculizumab therapy improved his hematologic findings without use of hemodialysis.

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.

ATYPICAL HEMOLYTIC UREMIC SYNDROME IN CHILDREN: PRACTICAL ASPECTS OF DIFFERENTIAL DIAGNOSTICS AND TREATMENT

2021 ◽  
Vol 100 (4) ◽  
pp. 64-73
Author(s):  
S.V. Baiko ◽  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Alternative Pathway ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Differential Diagnostics ◽  
E Coli ◽  
Uremic Syndrome ◽  
Stage Renal Disease ◽  
End Stage ◽  
The Complement System ◽  
Terminal Complement

Atypical hemolytic uremic syndrome (aHUS) is a rare progressive form of systemic thrombotic microangiopathy (TMA) that develops as a result of uncontrolled activation of the alternative pathway of the complement system. In the case of late diagnosis and inadequate treatment, aHUS has an unfavorable outcome with death rates as high as 25% during the acute phase and up to 50% of cases progressing to end-stage renal disease. Clinically, aHUS is very similar to disseminated intravascular coagulation, other TMAs: HUS associated with enterohemorrhagic E. coli, thrombotic thrombocytopenic purpura, etc. The article presents the sequence and scope of studies for the differential diagnosis of aHUS. Eculizumab and its biosimilars, blocking the terminal complement complex, have changed the future of patients with aHUS, so timely diagnosis and early treatment are crucial in the outcome of the disease.

Atypical Hemolytic Uremic Syndrome, Genetic Basis, and Clinical Manifestations

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 15-20 ◽  
Author(s):  
David Kavanagh ◽  
Timothy H. J. Goodship
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Clinical Manifestations ◽  
Factor H ◽  
Complement Inhibitors ◽  
Alternative Complement ◽  
Genes Encoding ◽  
Uremic Syndrome ◽  
End Stage ◽  
Acquired Abnormalities

Abstract Atypical hemolytic uremic syndrome (aHUS) is now well recognized to be a disease characterized by excessive complement activation in the microvasculature. In both the familial and sporadic forms, inherited and acquired abnormalities affecting components of the alternative complement pathway are found in ∼ 60% of patients. These include mutations in the genes encoding both complement regulators (factor H, factor I, membrane cofactor protein, and thrombomodulin) and activators (factors B and C3) and autoantibodies against factor H. Multiple hits are necessary for the disease to manifest, including a trigger, mutations, and at-risk haplotypes in complement genes. The prognosis for aHUS is poor, with most patients developing end-stage renal failure. Renal transplantation in most patients also has a poor prognosis, with frequent loss of the allograft to recurrent disease. However, improving results with combined liver-kidney transplantation and the advent of complement inhibitors such as eculizumab offer hope that the prognosis for aHUS will improve in future years.

scholarly journals Hemolytic Uremic Syndrome Caused by Mycoplasma Pneumoniae Infection in Children: A Case Report and Literature Review

2021 ◽  
Author(s):  
Sirinthip Kittivisuit ◽  
Prayong Vachvanichsanong ◽  
Thirachit Chotsampancharoen
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Hemolytic Anemia ◽  
Mycoplasma Pneumoniae ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Renal Dialysis ◽  
Microangiopathic Hemolytic Anemia ◽  
Uremic Syndrome ◽  
Red Cell Transfusion ◽  
Stage Renal Disease ◽  
End Stage

We describe the case of a 6-year-old boy with a Mycoplasma pneumoniae (M. pneumoniae) respiratory tract infection associated with thrombotic microangiopathic hemolytic anemia and thrombocytopenia with renal failure which was diagnosed as atypical hemolytic uremic syndrome. Renal biopsy showed features of thrombotic microangiopathy. The patient was treated with azithromycin for the M. pneumoniae infection, and supportive care with red cell transfusion and renal dialysis in the acute period. The microangiopathic hemolytic anemia and thrombocytopenia resolved within 2 months after diagnosis but the renal function damage was irreversible. The patient developed end-stage renal disease and required long term renal replacement therapy.

Atypical hemolytic uremic syndrome & treatment: case study

2021 ◽  
pp. 1-7
Author(s):  
Azhar Ali Khan ◽  
Muhammad Usman Ahraf ◽  
Usman Javaid
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Kidney Injury ◽  
Daily Basis ◽  
Fresh Frozen Plasma ◽  
Atypical Hus ◽  
Fresh Frozen ◽  
Uremic Syndrome ◽  
Stage Renal Disease ◽  
End Stage

Abstract Atypical Hemolytic Uremic Syndrome (aHUS) is considered as an uncommon pathology that usually affects young adults and causes acute kidney injury which can further lead to End Stage Renal Disease (ESRD). Atypical HUS usually occurs due to impairment in alternate pathway of complement system. aHUS are usually sporadic and less than 20% cases are familial. About 50% aHUS cases show no clear initiating factors. Mortality rate has been reduced in atypical HUS over the years due to progress in intensive care and dialysis facility. First treatment option should be PE, with exchange of 1.5 plasma volumes (60-75 ml/kg) per session, under the cover of fresh frozen plasma (FFP). PE needs to be performed on daily basis while waiting for the results of platelet count, LDH and Hb levels to be normal and renal functions showing improvement. Here we present a case in 15-year-old boy who was healthy previously. Continuous...

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