Indunil Karunarathna: A Comprehensive New Guide to Haemolytic Uremic Syndrome
Indunil Karunarathna, Founder of Uva Clinical Research Lab (UCRL), shared a post on LinkedIn:
“Haemolytic Uremic Syndrome: A Clinician’s Guide to Pathophysiological Subtypes, Diagnostic Differentiation, and Targeted Therapy (Dr Indunil Karunarathna Uva Clinical Research Lab 2026, Uva Clinical Anaesthesia and Intensive Care ISSN 2827-7198, 2026)
Haemolytic uremic syndrome (HUS) is a potentially catastrophic thrombotic microangiopathy defined clinically by the triad of microangiopathic hemolytic anemia, profound thrombocytopenia, and acute kidney injury.
Beneath this unified clinical presentation lies a spectrum of distinct etiologies, each with unique pathophysiological drivers, natural histories, and therapeutic implications.
Typical HUS, most often triggered by Shiga toxin–producing Escherichia coli (STEC), follows a diarrheal prodrome and generally responds to aggressive supportive care, including volume resuscitation and blood product support as needed.
In contrast, atypical HUS (aHUS) arises from uncontrolled alternative complement pathway activationtypically due to genetic mutations in regulatory proteins such as Factor H, Factor I, or membrane cofactor protein, or to acquired autoantibodiesand carries a high risk of progressive end-stage renal disease and mortality if not treated promptly with terminal complement inhibitors such as eculizumab or ravulizumab.
Secondary HUS encompasses cases driven by underlying conditions, including Streptococcus pneumoniae infection, autoimmune disease, malignancy, certain medications, or pregnancy, and requires treatment of the primary trigger often supplemented by complement blockade.
Differentiating among these subtypes is not an academic nicety but a clinical necessity, as management strategies differ fundamentally:
antibiotics and antimotility agents are avoided in STEC-HUS but may be indicated in other contexts, whereas complement inhibitors are life-saving in aHUS yet play no role in typical disease.
This review provides a conceptually grounded, clinically actionable framework for recognizing, evaluating, and managing HUS across the age spectrum, with emphasis on the pathophysiological rationale guiding each decision and the interprofessional collaboration essential for optimal outcomes.”
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