Atypical hemolytic uremic syndrome: A case-based review

Abstract

Atypical hemolytic uremic syndrome (aHUS) is an uncommon but potentially fatal form of thrombotic microangiopathy driven by dysregulation of the alternative complement pathway, frequently linked to genetic alterations affecting complement-regulatory proteins. Its clinical presentation is heterogeneous and overlaps with other thrombotic microangiopathies, frequently delaying diagnosis and increasing the risk of irreversible organ damage. Advances in complement biology have substantially improved understanding of disease mechanisms and enabled the development of targeted C5 inhibitors, which have transformed patient outcomes. This review summarizes current knowledge regarding the epidemiology, genetic landscape, pathophysiology, clinical manifestations, diagnostic approach, and contemporary management of aHUS, with particular emphasis on complement inhibition strategies. The discussion is contextualized by a representative clinical case illustrating real-world diagnostic complexity, systemic involvement, and therapeutic decision-making. Evidence indicates that both eculizumab and ravulizumab provide effective and sustained complement blockade, with ravulizumab offering extended dosing intervals and potential advantages in treatment burden and patient preference. Despite therapeutic progress, important challenges remain, including early recognition, interpretation of complex genetic findings, determination of optimal treatment duration, and discontinuation strategies. Continued research and improved epidemiological surveillance are essential to refine risk stratification and optimize long-term outcomes in this rare but severe complement-mediated disorder.

Keywords

Atypical hemolytic uremic syndrome / Ravulizumab / Thrombotic microangiopathy / Atypical hemolytic uremic syndrome

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