Duration of prodromal phase and severity of hemolytic uremic syndrome.

Background: Some data have recognized an association between shorter prodromal phase and severe episode of Shiga toxin-producing Escherichia coli-related hemolytic uremic syndrome (STEC-HUS). Our aims were to confirm such association and analyze characteristics of STEC-HUS patients according to duration of the prodromal phase.

Methods: Patients treated from 2000 to 2022 were compared according to the presence of severe (> 10 days of dialysis and/or extra-renal complications) or non-severe disease. Association between prodromal phase duration and disease severity was assessed by ROC curve and by classifying the cohort in 3 groups according to time to diagnosis.

Results: Non-severe (n = 145) and severe (n = 71) cases were compared. The latter had shorter prodromal phase, higher leukocyte count, hemoglobin, lactic dehydrogenase, liver enzymes, C-reactive protein, urea and creatinine, and lower albumin and sodium; only prodromal phase duration (p = 0.02) and leukocyte count (p = 0.02) remained significant in multivariate analysis. By ROC curve analysis, time to diagnosis resulted in a poor predictor of outcomes (AUC = 0.27). Since prodromal phase duration was 5 days (IQR 3-7), we divided the cohort into Groups A (1-2 days), B (3-7 days), and C (≥ 8 days). Rates of severe disease were 75.8%, 29.6%, and 11.4%, respectively. Taking Group B as reference, Group A patients had higher risk of complications (p = 0.00001; OR 7.4, 95% CI: 2.98-18.7) while Group C ones had significantly less risk (p = 0.02; OR 0.3, 95% CI: 0.1-0.91).

Conclusions: This study found that duration of prodromal phase is an independent predictor of complicated STEC-HUS and confirms that shorter prodromal phase is associated with worse prognosis. A higher resolution version of the Graphical abstract is available as Supplementary information.