Interventions for preventing diarrhoea-associated haemolytic uraemic syndrome.

Abstract

Background: Haemolytic uraemic syndrome (HUS) is a common cause of acquired kidney failure in children and rarely in adults. The most important risk factor for the development of HUS is a gastrointestinal infection by Shiga toxin-producing Escherichia coli (STEC). This is an update of the Cochrane review published in 2021 and addresses the interventions aimed at secondary prevention of HUS in patients with diarrhoea who are infected with bacteria that increase the risk of HUS.

Objectives: To assess the benefits and harms of interventions for secondary prevention of morbidity and death from diarrhoea-associated HUS in children and adults, compared to placebo or no treatment.

Search methods: The Cochrane Kidney and Transplant Register of Studies was searched up to January 2025 by the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov.

Selection criteria: Studies evaluating any intervention to prevent HUS following the development of high-risk diarrhoeal illness were included. These included interventions such as antibiotics, anti-Shiga toxin monoclonal antibodies, Shiga toxin binding protein (i.e. Synsorb Pk), bovine colostrum containing Shiga toxin antibodies, and aggressive hydration. The comparison groups included placebo and standard care. Only randomised controlled trials (RCTs) or quasi-RCTs were considered eligible for inclusion. The participants of the studies were children and adults with diarrhoeal illnesses due to STEC.

Data collection and analysis: We used standard methodological procedures as recommended by Cochrane. Summary estimates of effect were obtained using a random-effects model, and results were expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes. The primary outcome of interest was the incidence of HUS; secondary outcomes included kidney failure, need for acute kidney replacement therapy (KRT), need for prolonged dialysis, all-cause death, adverse events, need for blood product transfusions and neurological complications. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Main results: For this 2025 update, no new studies were included. In the 2021 review, we identified four studies (536 participants) undertaken in three countries (Argentina, Canada, Germany) that investigated four different interventions, including antibiotics (trimethoprim-sulfamethoxazole), bovine colostrum containing Shiga toxin antibodies, Shiga toxin binding agent (Synsorb Pk: a silicon dioxide-based agent), and a monoclonal antibody against Shiga toxin (urtoxazumab). The overall risk of bias was unclear for selection, performance and detection bias and low for attrition, reporting and other sources of bias. It was uncertain if antibiotics (trimethoprim-sulfamethoxazole) reduced the incidence of HUS compared to no treatment (47 participants: RR 0.57, 95% CI 0.11 to 2.81; very low-certainty evidence). Adverse events relative to this review, need for KRT, neurological complications and death were not reported. There were no incidences of HUS in either the bovine colostrum group or the placebo group. It was uncertain if bovine colostrum caused more adverse events (27 participants: RR 0.92, 95% CI 0.42 to 2.03; very low-certainty evidence). The need for KRT, neurological complications and death were not reported. It is uncertain whether Synsorb Pk reduced the incidence of HUS compared to placebo (353 participants: RR 0.93, 95% CI 0.39 to 2.22; very low-certainty evidence). Adverse events relevant to this review, need for KRT, neurological complications and death were not reported. One study compared two doses of urtoxazumab (3.0 mg/kg and 1.0 mg/kg) to placebo. It is uncertain if either 3.0 mg/kg urtoxazumab (71 participants: RR 0.34, 95% CI 0.01 to 8.14) or 1.0 mg/kg urtoxazumab (74 participants: RR 0.95, 95% CI 0.06 to 14.59) reduced the incidence of HUS compared to placebo (very low-certainty evidence). Low-certainty evidence showed there may be little or no difference in the number of treatment-emergent adverse events with either 3.0 mg/kg urtoxazumab (71 participants: RR 1.00, 95% CI 0.84 to 1.18) or 1.0 mg/kg urtoxazumab (74 participants: RR 0.95, 95% CI 0.79 to 1.13) compared to placebo. It is uncertain if either dose of urtoxazumab increased the risk of neurological complications or death (very low-certainty evidence). The need for KRT was not reported.

Authors' conclusions: The included studies assessed antibiotics, bovine colostrum, Shiga toxin binding agent (Synsorb Pk) and monoclonal antibodies (Urtoxazumab) against Shiga toxin for secondary prevention of HUS in patients with diarrhoea due to STEC. However, no firm conclusions about the benefits or harms of these interventions can be drawn given the small number of included studies and the small sample sizes of those included studies. Additional studies, including larger multicentre studies, are needed to assess the benefits and harms of interventions to prevent the development of HUS in patients with diarrhoea due to STEC infection. No new studies were included in this 2025 update, and the results remain unchanged.