At the Cross Section of Thrombotic Microangiopathy and Atypical Hemolytic Uremic Syndrome: A Narrative Review of Differential Diagnostics and a Problematization of Nomenclature

Abstract

Complement-mediated atypical hemolytic uremic syndrome (aHUS) is a rare disease associated with high mortality and morbidity. Renal biopsies often indicate thrombotic microangiopathy (TMA). The condition is caused by an excessive activation of the alternative pathway leading to depositions of membrane attack complexes (MAC) on host cells. It may depend on mutations in complement components and regulatory proteins, or the formation of complement-specific antibodies. Mainly, an environmental trigger (e.g. infection) is needed for the excessive response to develop. The clinical characteristics are more or less shared with a wide range of diseases manifesting with microangiopathic hemolytic anemia. Because of prior deficits in pathogenic understanding, associated nomenclature has been based on clinical symptoms. New knowledge challenges these symptomatic definitions; however, an outdated terminology is still being applied in clinical practice to various extents. With respect to gained insights, it is more advantageous to rebuild the concepts on etiological and pathogenic grounds. The need for more distinct definitions is even more urgent in the light of the effective treatment regimen with eculizumab for complement-mediated aHUS. This review presents an up-to-date summary of the field of investigation, addresses the need for faster differential diagnostics and proposes a revised nomenclature based on the current pathogenic understanding.