scholarly journals Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome

Blood ◽  
2006 ◽  
Vol 108 (4) ◽  
pp. 1267-1279 ◽  
Author(s):  
Jessica Caprioli ◽  
Marina Noris ◽  
Simona Brioschi ◽  
Gaia Pianetti ◽  
Federica Castelletti ◽  
...  
Keyword(s):  
Disease Recurrence ◽  
Factor H ◽  
Response To Therapy ◽  
Regulatory Proteins ◽  
Response To Treatment ◽  
Complement Factor ◽  
Genetic Studies ◽  
Complement Regulatory Proteins ◽  
Uremic Syndrome ◽  
The Impact

Abstract Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy with manifestations of hemolytic anemia, thrombocytopenia, and renal impairment. Genetic studies have shown that mutations in complement regulatory proteins predispose to non–Shiga toxin–associated HUS (non-Stx–HUS). We undertook genetic analysis on membrane cofactor protein (MCP), complement factor H (CFH), and factor I (IF) in 156 patients with non-Stx–HUS. Fourteen, 11, and 5 new mutational events were found in MCP, CFH, and IF, respectively. Mutation frequencies were 12.8%, 30.1%, and 4.5% for MCP, CFH, and IF, respectively. MCP mutations resulted in either reduced protein expression or impaired C3b binding capability. MCP-mutated patients had a better prognosis than CFH-mutated and nonmutated patients. In MCP-mutated patients, plasma treatment did not impact the outcome significantly: remission was achieved in around 90% of both plasma-treated and plasma-untreated acute episodes. Kidney transplantation outcome was favorable in patients with MCP mutations, whereas the outcome was poor in patients with CFH and IF mutations due to disease recurrence. This study documents that the presentation, the response to therapy, and the outcome of the disease are influenced by the genotype. Hopefully this will translate into improved management and therapy of patients and will provide the way to design tailored treatments.

scholarly journals Pediatric Atypical Hemolytic Uremic Syndrome Advances

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3580
Author(s):  
Rupesh Raina ◽  
Nina Vijayvargiya ◽  
Amrit Khooblall ◽  
Manasa Melachuri ◽  
Shweta Deshpande ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Factor H ◽  
Regulatory Proteins ◽  
High Rate ◽  
Complement Factor ◽  
Mortality And Morbidity ◽  
Complement Regulatory Proteins ◽  
Alternate Pathway ◽  
Uremic Syndrome

Atypical hemolytic uremic syndrome (aHUS) is a rare disorder characterized by dysregulation of the alternate pathway. The diagnosis of aHUS is one of exclusion, which complicates its early detection and corresponding intervention to mitigate its high rate of mortality and associated morbidity. Heterozygous mutations in complement regulatory proteins linked to aHUS are not always phenotypically active, and may require a particular trigger for the disease to manifest. This list of triggers continues to expand as more data is aggregated, particularly centered around COVID-19 and pediatric vaccinations. Novel genetic mutations continue to be identified though advancements in technology as well as greater access to cohorts of interest, as in diacylglycerol kinase epsilon (DGKE). DGKE mutations associated with aHUS are the first non-complement regulatory proteins associated with the disease, drastically changing the established framework. Additional markers that are less understood, but continue to be acknowledged, include the unique autoantibodies to complement factor H and complement factor I which are pathogenic drivers in aHUS. Interventional therapeutics have undergone the most advancements, as pharmacokinetic and pharmacodynamic properties are modified as needed in addition to their as biosimilar counterparts. As data continues to be gathered in this field, future advancements will optimally decrease the mortality and morbidity of this disease in children.

FIRST EXPERIENCE OF USING THE BIOSIMILAR OF ORIGINAL ECULIZUMAB FOR PREVENTION OF ATYPICAL HEMOLYTIC-UREMIC SYNDROME RECURRENCE AFTER RENAL TRANSPLANTATION IN A CHILD

2021 ◽  
Vol 100 (1) ◽  
pp. 293-296
Author(s):  
S.V. Baiko ◽  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Molecular Genetic ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Disease Recurrence ◽  
Regulatory Proteins ◽  
Molecular Genetic Study ◽  
Complement Regulatory Proteins ◽  
Before And After ◽  
Uremic Syndrome ◽  
End Stage

The article presents a clinical case of atypical hemolytic uremic syndrome (аHUS), the debut of which proceeded under the guise of a typical HUS. After 4 months of hemodialysis, the child did not need renal replacement therapy for the next 9 months. The development of end-stage renal failure required a molecular genetic study to clarify the diagnosis. The child has mutations in the genes of the complement regulatory proteins – factor I and MCP. The risk of aHUS recurrence with these genes mutations to a renal transplant without pathogenetic prophylaxis is up to 80%. The use of the Russian biosimilar eculizumab before and after kidney transplantation allowed to prevent the activation of complement and disease recurrence to transplanted organ.

Outcomes of renal transplant in patients with anti-complement factor H antibody-associated hemolytic uremic syndrome

2014 ◽  
Vol 18 (5) ◽  
pp. E134-E139 ◽  
Author(s):  
Priyanka Khandelwal ◽  
Aditi Sinha ◽  
Pankaj Hari ◽  
Virinder K. Bansal ◽  
Amit K. Dinda ◽  
...  
Keyword(s):  
Renal Transplant ◽  
Hemolytic Uremic Syndrome ◽  
Factor H ◽  
Complement Factor H ◽  
Complement Factor ◽  
Uremic Syndrome

Atypical Hemolytic Uremic Syndrome Associated with Complement Factor H Mutation and IgA Nephropathy: A Case Report Successfully Treated with Eculizumab

Nephron ◽  
2017 ◽  
Vol 138 (4) ◽  
pp. 324-327 ◽  
Author(s):  
Hironori Nakamura ◽  
Mariko Anayama ◽  
Mutsuki Makino ◽  
Yasushi Makino ◽  
Katsuhiko Tamura ◽  
...  
Keyword(s):  
Case Report ◽  
Hemolytic Uremic Syndrome ◽  
Iga Nephropathy ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Factor H ◽  
Complement Factor H ◽  
Complement Factor ◽  
Uremic Syndrome ◽  
Factor H Mutation

scholarly journals De Novo Atypical Haemolytic Uremic Syndrome after Kidney Transplantation

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Arnaud Devresse ◽  
Martine de Meyer ◽  
Selda Aydin ◽  
Karin Dahan ◽  
Nada Kanaan
Keyword(s):  
Kidney Transplantation ◽  
De Novo ◽  
Alternative Pathway ◽  
Factor H ◽  
Complement Factor ◽  
Haemolytic Uremic Syndrome ◽  
Hinman Syndrome ◽  
Uremic Syndrome ◽  
Stage Renal Disease ◽  
End Stage

De novo thrombotic microangiopathy (TMA) can occur after kidney transplantation. An abnormality of the alternative pathway of complement must be suspected and searched for, even in presence of a secondary cause. We report the case of a 23-year-old female patient who was transplanted with a kidney from her mother for end-stage renal disease secondary to Hinman syndrome. Early after transplantation, she presented with 2 episodes of severe pyelonephritis, associated with acute kidney dysfunction and biological and histological features of TMA. Investigations of the alternative pathway of the complement system revealed atypical haemolytic uremic syndrome secondary to complement factor I mutation, associated with mutations in CD46 and complement factor H related protein genes. Plasma exchanges followed by eculizumab injections allowed improvement of kidney function without, however, normalization of creatinine.

scholarly journals Case Report: Lipoprotein Glomerulopathy Complicated by Atypical Hemolytic Uremic Syndrome

2021 ◽  
Vol 8 ◽  
Author(s):  
Lara Kollbrunner ◽  
Patricia Hirt-Minkowski ◽  
Javier Sanz ◽  
Elena Bresin ◽  
Thomas J. Neuhaus ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Factor H ◽  
Complement Factor ◽  
Inherited Disease ◽  
Lipoprotein Glomerulopathy ◽  
Gene Encoding ◽  
Alternative Complement ◽  
Uremic Syndrome ◽  
The Complement System

Lipoprotein glomerulopathy (LPG) is a rare inherited disease caused by mutations in the APOE gene, encoding apolipoprotein E (apoE). Atypical hemolytic uremic syndrome (aHUS) is a thrombotic microangiopathy (TMA) characterized by overactivation of the alternative complement pathway. Here we report the case of a 21-year-old man with LPG who developed aHUS. A functional complement assay demonstrated an overactivation of the complement system. Complementary genetic analysis revealed a homozygous aHUS risk allele for complement factor-H related 1 (CFHR1), CFHR1*B. To the best of our knowledge, this is the first report of an aHUS in a patient with LPG.

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