Approach

Consultation with nephrology and haematology specialists in management of HUS is recommended.[48]

Shiga toxin-producing Escherichia coli (STEC) HUS

Children with the typical presentation of bloody diarrhoea, abdominal pain, nausea, and vomiting should be hospitalised. This can expedite evaluation, and maintenance of intravascular volume, and thus possibly decrease the risk of complications and the risk of transmission.[8][49]

Treatment is primarily supportive. Early intravascular fluid repletion reduces the frequency of oligoanuric acute kidney injury in patients with pre-HUS diarrhoea and appears to improve outcomes in children with diarrhoea-positive HUS.[50][51] Meticulous attention should be paid to fluid balance and monitoring urine output; care should be taken to avoid cardiopulmonary overload because these patients are at risk of developing oliguria.[45][52]

Blood pressure should be monitored and treated if elevated. Hypertension can occur secondary to multiple factors, including volume overload, electrolyte imbalances, and underlying thrombotic microangiopathy affecting the kidneys. Calcium-channel blockers, vasodilators, and beta-blockers can be used in the acute phase for the treatment of hypertension.[53] ACE inhibitors are not generally recommended in the acute setting because of concerns of decreased renal perfusion, but are recommended for patients with end-stage renal disease post HUS.[54][55]

Systematic reviews have found no significant effect for antibiotic therapy, anti‐Shiga toxin antibody‐containing bovine colostrum, Shiga toxin binding agent (Synsorb Pk), or urtoxazumab (a monoclonal antibody against Shiga toxin) for the secondary prevention of HUS in patients with STEC-associated diarrhoea (very low-quality evidence).[30][56]

Although there are insufficient data on the effect of opioids on the course of HUS, cautious use of opioids is advised.

Some interventions may increase risk for HUS and irreversible renal damage.

Avoidance of antibiotics, antimotility (antidiarrhoeal) agents, and non-steroidal anti-inflammatory drugs is advised in children presenting with bloody diarrhoea.

Trimethoprim-sulfamethoxazole showed no significant effect for secondary prevention of HUS in patients with STEC (very low-quality evidence).[30][56] Antibiotic administration for STEC infections is not recommended because of the potentially increased risk for HUS reported in observational studies.[57][58]

Administration of antimotility agents may increase risk for HUS in patients with diarrhoea caused by STEC infections; worsening clinical condition, including central nervous system (CNS) complications, has been reported.[59][60][61]

Platelet transfusions have been associated with clinical deterioration and should be avoided unless there is active bleeding.[62]

Red cell transfusion, dialysis, and renal transplantation

Anaemia is common and can be rapid in onset, requiring red cell transfusion. Approximately 50% of patients will require dialysis in the acute phase.[61][63][64] Patients who develop irreversible acute kidney injury are considered for renal transplantation.

Extra-renal involvement should be assessed, given its contribution to morbidity and mortality:[65][66][67][68][69]

  • CNS involvement can lead to stroke or haemorrhage and in rare cases, brain abscesses

  • Pancreatic involvement, in the form of pancreatitis or acute-onset insulin-dependent diabetes mellitus, can occur, along with bowel infarction, ischaemia, or necrosis

  • Cardiac involvement in the form of impaired cardiac contractility and myocarditis can occur

  • Ocular and hepatic involvement, although rare, have been reported in diarrhoea-positive HUS.

Treatment of atypical HUS

Atypical HUS (aHUS) should be suspected when other causes have been ruled out.

Evaluation of the alternative complement pathway can reveal the cause of aHUS. However, to date there is no direct diagnostic test for detecting aHUS.[5]

The diagnosis of aHUS can be more challenging in adults due to other clinical conditions that can present in a similar fashion. Treatment should not be delayed while awaiting genetic test results; plasma exchange is appropriate in adults (particularly if thrombotic thrombocytopenic purpura remains a possibility).

Eculizumab

A monoclonal antibody that binds to C5 complement protein and blocks terminal complement activation, eculizumab is approved for the management of aHUS in children and adults. Systematic reviews of small non‐randomised, single‐arm studies indicate that eculizumab improves kidney function in patients with aHUS.[70][71][72] Randomised controlled trials of patients with aHUS are unlikely; careful design of subsequent single-arm trials, in addition to long-term follow-up, are required.[70][72]

Meningococcal prophylaxis is required because there is a risk of infection with encapsulated organisms in patients treated with eculizumab. Eculizumab is contraindicated in patients with unresolved Neisseria meningitidis infection, and in those who are not currently vaccinated against N meningitidis unless the risks of delaying treatment outweigh the risks of developing an infection. Patients who have not been previously vaccinated should be vaccinated against N meningitidis at least 2 weeks before starting treatment with eculizumab. All patients should be re-vaccinated according to current local vaccination guidelines for patients with complement deficiencies.

Treatment of secondary HUS

Secondary HUS associated with chemotherapy or bone marrow transplant generally has a poor prognosis, and the response to plasma exchange or terminal complement inhibition (e.g., eculizumab) has not been established.

Dialysis is performed for patients with acute kidney injury. Renal transplantation can be done for patients with irreversible acute kidney injury. Eculizumab may be required post renal transplantation to prevent recurrence of disease in the allograft.[70][71][73][74]

Treatment of Streptococcus pneumoniae-associated HUS

Plasma exchange is contraindicated in patients with Streptococcus pneumoniae-associated HUS because the infusion of plasma containing naturally occurring antibodies against the Thomsen-Friedenreich antigen could worsen the agglutination.[16]

Patients with streptococcal infection should be treated with appropriate antibiotics according to local protocols and antibiotic sensitivities.

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