First Episode of STEC and Non-STEC Hemolytic Uremic Syndrome in Children: Predictors of Severe Complications and Mortality From a Single-Center Cohort

<title>Abstract</title> <p>Background Hemolytic uremic syndrome (HUS) is the leading cause of acute kidney injury in children. Early differentiation between Shiga toxin-producing Escherichia coli (STEC-HUS) and atypical/non-STEC HUS (aHUS) is essential because these entities differ in pathophysiology, treatment, and prognosis. Methods 94 children diagnosed with HUS between 2015 and 2025 (STEC-HUS: 66; non-STEC HUS: 28) were retrospectively analyzed. Clinical, microbiological, laboratory, therapeutic, and outcome data were compared. Univariable and multivariable logistic regression analyses identified predictors of neurological involvement and mortality. Results STEC-HUS was associated with a typical gastrointestinal prodrome, including diarrhea, abdominal pain, and Shiga toxin positivity (p &lt; 0.05), whereas preceding respiratory tract infections occurred more frequently in the non-STEC HUS group (50% vs 19.7%, p:0.004). Patients with non-STEC HUS had a significantly more severe clinical course, with higher rates of kidney replacement therapy (75% vs 51.5%, p:0.028), hypertension (78.6% vs 47%, p:0.004) and neurological involvement (57.1% vs 28.8%, p:0.009). Neurological manifestations were strongly associated with non-STEC HUS; seizures showed the strongest association, increasing the odds of non-STEC disease more than 4-fold (OR 4.57, p:0.049). Independent predictors of mortality included low admission C3 levels, elevated CRP and D-dimer concentrations, while ischemic stroke (AOR 12.53, p:0.030) and bulbar symptoms (AOR 36.09, p:0.016) were the strongest neurological predictors of death. Conclusions Non-STEC HUS represents a more severe multisystem disorder than STEC-HUS. The characteristic gastrointestinal prodrome of STEC-HUS may facilitate early differentiation, whereas neurological manifestations should raise suspicion of complement-mediated HUS.</p>