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

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.

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

Kidney International ◽

10.1016/j.kint.2016.10.005 ◽

2017 ◽

Vol 91 (3) ◽

pp. 539-551 ◽

Cited By ~ 217

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

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

Journal of the American Society of Nephrology ◽

10.1681/asn.2019050515 ◽

2020 ◽

Vol 31 (2) ◽

pp. 241-256 ◽

Cited By ~ 9

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.

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