Genetic and Protein Structural Evaluation of Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy

2020 ◽  
Vol 27 (2) ◽  
pp. 120-127.e4 ◽  
Author(s):  
Stephen J. Perkins
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
C3 Glomerulopathy ◽  
Structural Evaluation ◽  
Uremic Syndrome

scholarly journals CFHR Gene Variations Provide Insights in the Pathogenesis of the Kidney Diseases Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy

2020 ◽  
Vol 31 (2) ◽  
pp. 241-256 ◽  
Author(s):  
Peter F. Zipfel ◽  
Thorsten Wiech ◽  
Emma D. Stea ◽  
Christine Skerka
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Kidney Diseases ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Human Kidney ◽  
Copy Number Variations ◽  
Factor H ◽  
C3 Glomerulopathy ◽  
Hybrid Proteins ◽  
Genetic Modifications ◽  
Uremic Syndrome

Sequence and copy number variations in the human CFHR–Factor H gene cluster comprising the complement genes CFHR1, CFHR2, CFHR3, CFHR4, CFHR5, and Factor H are linked to the human kidney diseases atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy. Distinct genetic and chromosomal alterations, deletions, or duplications generate hybrid or mutant CFHR genes, as well as hybrid CFHR–Factor H genes, and alter the FHR and Factor H plasma repertoire. A clear association between the genetic modifications and the pathologic outcome is emerging: CFHR1, CFHR3, and Factor H gene alterations combined with intact CFHR2, CFHR4, and CFHR5 genes are reported in atypical hemolytic uremic syndrome. But alterations in each of the five CFHR genes in the context of an intact Factor H gene are described in C3 glomerulopathy. These genetic modifications influence complement function and the interplay of the five FHR proteins with each other and with Factor H. Understanding how mutant or hybrid FHR proteins, Factor H::FHR hybrid proteins, and altered Factor H, FHR plasma profiles cause pathology is of high interest for diagnosis and therapy.

scholarly journals Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference

2017 ◽  
Vol 91 (3) ◽  
pp. 539-551 ◽  
Author(s):  
Timothy H.J. Goodship ◽  
H. Terence Cook ◽  
Fadi Fakhouri ◽  
Fernando C. Fervenza ◽  
Véronique Frémeaux-Bacchi ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
C3 Glomerulopathy ◽  
Uremic Syndrome

ATYPICAL HEMOLYTIC UREMIC SYNDROME AND C3 GLOMERULOPATHY: CONCLUSIONS FROM A «KIDNEY DISEASE: IMPROVING GLOBAL OUTCOMES» (KDIGO) CONTROVERSIES CONFERENCE

2018 ◽  
Vol 22 (4) ◽  
pp. 18-39
Author(s):  
Timothy H.J. Goodship ◽  
H. Terence Cook ◽  
Fadi Fakhouri ◽  
Fernando C. Fervenza ◽  
Veronique Fremeaux-Bacchi ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Hemolytic Uremic Syndrome ◽  
Treatment Options ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Treatment Strategies ◽  
Evidence Base ◽  
Current Treatment ◽  
Primary Role ◽  
C3 Glomerulopathy ◽  
Uremic Syndrome

In both atypical hemolytic uremic syndrome (aHUS) and C3 glomerulopathy (C3G) complement plays a primary role in disease pathogenesis. Herein we report the outcome of a 2015  Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference where key issues in the management of  these 2 diseases were considered by a global panel of experts. Areas addressed included renal pathology, clinical phenotype and  assessment, genetic drivers of disease, acquired drivers of disease, and treatment strategies. In order to help guide clinicians  who are caring for such patients, recommendations for best  treatment strategies were discussed at length, providing the  evidence base underpinning current treatment options. Knowledge gaps were identified and a prioritized research agenda  was proposed to resolve outstanding controversial issues. 

scholarly journals Case report: C3 glomerulopathy advancing atypical hemolytic uremic syndrome

Nefrología ◽  
2018 ◽  
Vol 38 (4) ◽  
pp. 450-452 ◽  
Author(s):  
Muge Catikkas ◽  
Erol Demir ◽  
Yasemin Ozluk ◽  
Yasar Caliskan ◽  
Rabia Muberra Badur ◽  
...  
Keyword(s):  
Case Report ◽  
Hemolytic Uremic Syndrome ◽  
Atypical Hemolytic Uremic Syndrome ◽  
C3 Glomerulopathy ◽  
Uremic Syndrome

scholarly journals C3 Glomerulopathy and Atypical Hemolytic Uremic Syndrome: Two Important Manifestations of Complement System Dysfunction

2018 ◽  
Vol 8 (1) ◽  
pp. 25-34 ◽  
Author(s):  
Ravneet Bajwa ◽  
John A. DePalma ◽  
Taimoor Khan ◽  
Anmol Cheema ◽  
Sheila A. Kalathil ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Hemolytic Uremic Syndrome ◽  
Renal Dysfunction ◽  
Female Patient ◽  
Alternative Pathway ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Organ Injury ◽  
C3 Glomerulopathy ◽  
Kidney Involvement ◽  
Uremic Syndrome

The advances in our understanding of the alternative pathway have emphasized that uncontrolled hyperactivity of this pathway causes 2 distinct disorders that adversely impact the kidney. In the so-called atypical hemolytic uremic syndrome (aHUS), renal dysfunction occurs along with thrombocytopenia, anemia, and target organ injury to multiple organs, most commonly the kidney. On the other hand, in the so-termed C3 glomerulopathy, kidney involvement is not associated with thrombocytopenia, anemia, or other system involvement. In this report, we present 2 cases of alternative pathway dysfunction. The 60-year-old female patient had biopsy-proven C3 glomerulopathy, while the 32-year-old female patient was diagnosed with aHUS based on renal dysfunction, thrombocytopenia, anemia, and normal ADAMTS-13 level. The aHUS patient was successfully treated with the monoclonal antibody (eculizumab) for complement blockade. The patient with C3 glomerulopathy did not receive the monoclonal antibody. In this patient, management focused on blood pressure and proteinuria control with an angiotensin-converting enzyme inhibitor. This article focuses on the clinical differences, pathophysiology, and treatment of aHUS and C3 glomerulopathy.

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