Key messages
• There is not enough evidence to determine the best method for preventing haemolytic uraemic syndrome (HUS) in patients with Shiga toxin-producing Escherichia coli (STEC)-associated diarrhoea.
• More studies with a larger group of patients are required before any recommendation can be made.
What is haemolytic uraemic syndrome?
Haemolytic uraemic syndrome (HUS) is a serious illness that primarily affects children and can have severe side effects such as anaemia (low red blood cell counts), kidney damage, brain damage, and death in some cases. HUS most commonly occurs as a complication of diarrhoeal illness caused by a particular form of Escherichia coli (E. coli) bacteria called Shiga toxin-producing E. coli (STEC). In the USA, there are about 2 cases per 100,000 children a year. Despite the severity of HUS, there are currently no standard practices for treating these patients other than supportive care. There has been an interest in interventions that may prevent the occurrence of HUS in children with diarrhoea who are infected with bacteria that increase the risk of HUS. Some of these interventions include antibiotics, Shiga toxin monoclonal antibodies (an antibody specifically designed to bind with Shiga toxin), Shiga toxin binding agent (i.e. Synsorb Pk), bovine colostrum containing Shiga toxin antibodies, and aggressive hydration.
What did we want to find out?
We wanted to find out which interventions would prevent HUS in individuals with diarrhoea infected with high-risk bacteria.
What did we do?
We searched for studies that assessed the benefits and harms of any treatment for the prevention of HUS in children or adults as compared to either no treatment or a treatment known to have no effect. We compared and summarised the results of these studies and rated our confidence in the information based on factors such as study methods and sizes.
What did we find?
We found four studies conducted in Argentina (1), Canada (2) and Germany (1) that included 536 children (ranging from 27 to 353) who had diarrhoea and were infected with high-risk bacteria. These studies looked at four different preventative treatments, including antibiotic therapy, anti-Shiga toxin antibody-containing bovine colostrum (a form of breast milk that is released by the mammary glands after giving birth), Shiga toxin binding agent (Synsorb Pk: a silicon dioxide-based agent) and a monoclonal antibody to Shiga toxin (urtoxazumab).
It was uncertain if treatment with antibiotics (trimethoprim-sulfamethoxazole) reduced the occurrence of HUS compared to no treatment, based on data from one study. Adverse events, the need for kidney replacement therapy (a medical treatment that replaces the normal function of the kidneys in patients with kidney failure), neurological complications (such as a stroke or seizures), and death were not reported.
One study investigating bovine colostrum for the prevention of HUS did not report any HUS events. It was uncertain if the use of bovine colostrum increased the risk of any adverse events. The need for kidney replacement therapy, neurological complications and death were not reported.
One study investigated whether Synsorb Pk reduces the incidence of HUS, and the results were uncertain about its benefits. The need for kidney replacement therapy, neurological complications and death were not reported.
One study investigated urtoxazumab for the prevention of HUS and studied two different doses (3.0 mg/kg and 1.0 mg/kg) and compared them to placebo. It was uncertain if either 3.0 mg/kg or 1.0 mg/kg urtoxazumab reduced the incidence of HUS compared to placebo. There may be little or no difference in the number of treatment-related adverse events with either of the two doses compared to placebo. The data were uncertain about the risk of neurological complications and death. The need for kidney replacement therapy was not reported.
What are the limitations of the evidence?
The included studies had small numbers of participants, and the results did not favour any one intervention to reduce the progression of the disease to HUS in patients who were infected with STEC. No new studies were included in this update of the review. The small number and size of the studies were limitations in this review. Not all the studies provided data about the outcomes we were interested in, and we are unsure about the results.
How up to date is the evidence?
The evidence is current to January 2025.
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.
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.
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.
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.
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.
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.
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.