Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

Shiga toxin-producing Escherichia coli (STEC) HUS

1st line – intravenous isotonic crystalloids

Back
ACUTE
|
Shiga toxin-producing Escherichia coli (STEC) HUS
1st line – 

intravenous isotonic crystalloids

Diarrhea is present in most cases.

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.[43][52] Maintenance of adequate hydration is important to minimize the likelihood of renal damage.

Avoidance of antibiotics, antimotility (antidiarrheal) agents, and nonsteroidal anti-inflammatory drugs is advised in children presenting with bloody diarrhea. Although there are insufficient data on the effect of opioids on the course of HUS, cautious use of opioids is advised.

Trimethoprim-sulfamethoxazole showed no significant effect for secondary prevention of HUS in patients with STEC (very low-quality evidence).[28][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 diarrhea caused by STEC infections; worsening clinical condition, including central nervous system 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]

Plus – red cell transfusion

Back
ACUTE
|
Shiga toxin-producing Escherichia coli (STEC) HUS
|
with anemia
Plus – 

red cell transfusion

Treatment recommended for ALL patients in selected patient group

Red cell transfusions should be given (as per guidelines) to ameliorate cardiovascular or respiratory symptoms or for severe anemia (hematocrit <18%).

Close attention should be paid to electrolytes, as a blood transfusion in the setting of active hemolysis and renal injury can result in severe and life-threatening hyperkalemia.

Plus – antihypertensives

Back
ACUTE
|
Shiga toxin-producing Escherichia coli (STEC) HUS
|
with hypertension
Plus – 

antihypertensives

Treatment recommended for ALL patients in selected patient group

Hypertension can occur secondary to increased intravascular volume, electrolyte abnormalities, and underlying thrombotic microangiopathy affecting the kidney.

Blood pressure should be controlled to avoid renal damage and posterior reversible encephalopathy syndrome.

Recommended agents include calcium-channel blockers, vasodilators, and beta-blockers.

ACE inhibitors are not generally recommended in the acute setting, because of concerns of decreased renal perfusion, but can be used once the acute phase of HUS has subsided to help preserve renal function.[54][55]

Plus – dialysis

Back
ACUTE
|
Shiga toxin-producing Escherichia coli (STEC) HUS
|
with acute kidney injury
Plus – 

dialysis

Treatment recommended for ALL patients in selected patient group

Dialysis is performed if clinically indicated: volume overload, oligoanuria, signs and symptoms of uremia, hyperkalemia, persistent severe acidosis (bicarbonate <10), hypertension secondary to volume overload that cannot be controlled with medical therapy, and necessity for transfusion in patients with volume overload and/or oliguria.[9]

Different modalities of dialysis are used including peritoneal dialysis, hemodialysis, and continuous veno-venous hemofiltration. The choice of modality varies depending on patient condition, institutional policy, and physician's discretion.

Plus – renal transplant

Back
ACUTE
|
Shiga toxin-producing Escherichia coli (STEC) HUS
|
with irreversible acute kidney injury
Plus – 

renal transplant

Treatment recommended for ALL patients in selected patient group

For patients who have developed irreversible acute kidney injury, renal transplant can be considered after a period on dialysis.[46] It is important to investigate thoroughly for atypical HUS in this subset of patients.

The risk of recurrence in patients with STEC HUS and end-stage renal disease ranges from 0% to 10%.[75]

atypical HUS

1st line – eculizumab or plasma exchange

Back
ACUTE
|
atypical HUS
1st line – 

eculizumab or plasma exchange

A monoclonal antibody that binds to C5 complement protein and blocks terminal complement activation, eculizumab is approved for the management of atypical HUS in children and adults. Systematic reviews of small nonrandomized, single‐arm studies indicate that eculizumab improves kidney function in patients with aHUS.[70][71][72] Randomized 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 revaccinated according to current local vaccination guidelines for patients with complement deficiencies.

Plasma exchange is appropriate in adults (particularly if thrombotic thrombocytopenic purpura remains a possibility) while awaiting genetic test results.

Primary options

eculizumab: children and adults: consult specialist for guidance on dose

Consider – intravenous isotonic crystalloids

Back
ACUTE
|
atypical HUS
Consider – 

intravenous isotonic crystalloids

Treatment recommended for SOME patients in selected patient group

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.[43][52] Maintenance of adequate hydration is important to minimize the likelihood of renal damage.

Avoidance of antibiotics, antimotility (antidiarrheal) agents, and nonsteroidal anti-inflammatory drugs is advised in children presenting with bloody diarrhea. Although there are insufficient data on the effect of opioids on the course of HUS, cautious use of opioids is advised.

Trimethoprim-sulfamethoxazole showed no significant effect for secondary prevention of HUS in patients with STEC (very low-quality evidence).[28][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 diarrhea caused by STEC infections; worsening clinical condition, including central nervous system 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]

Plus – red cell transfusion

Back
ACUTE
|
atypical HUS
|
with anemia
Plus – 

red cell transfusion

Treatment recommended for ALL patients in selected patient group

Red cell transfusions should be given (as per guidelines) to ameliorate cardiovascular or respiratory symptoms or for severe anemia (hematocrit <18%).

Close attention should be paid to electrolytes, as a blood transfusion in the setting of active hemolysis and renal injury can result in severe and life-threatening hyperkalemia.

Plus – antihypertensives

Back
ACUTE
|
atypical HUS
|
with hypertension
Plus – 

antihypertensives

Treatment recommended for ALL patients in selected patient group

Hypertension can occur secondary to increased intravascular volume, electrolyte abnormalities, and underlying thrombotic microangiopathy affecting the kidney.

Blood pressure should be controlled to avoid renal damage and posterior reversible encephalopathy syndrome.

Recommended agents include calcium-channel blockers, vasodilators, and beta-blockers.

ACE inhibitors are not generally recommended in the acute setting, because of concerns of decreased renal perfusion, but can be used once the acute phase of HUS has subsided to help preserve renal function.[54][55]

Plus – dialysis

Back
ACUTE
|
atypical HUS
|
with acute kidney injury
Plus – 

dialysis

Treatment recommended for ALL patients in selected patient group

Dialysis is performed if clinically indicated: volume overload, oligoanuria, signs and symptoms of uremia, hyperkalemia, persistent severe acidosis (bicarbonate <10), hypertension secondary to volume overload that cannot be controlled with medical therapy, and necessity for transfusion in patients with volume overload and/or oliguria.[9]

Different modalities of dialysis are used including peritoneal dialysis, hemodialysis, and continuous veno-venous hemofiltration. The choice of modality varies depending on patient condition, institutional policy, and physician's discretion.

Plus – renal transplant

Back
ACUTE
|
atypical HUS
|
with irreversible acute kidney injury
Plus – 

renal transplant

Treatment recommended for ALL patients in selected patient group

For patients who have developed irreversible acute kidney injury, renal transplant can be considered.[46]

Eculizumab may be required post renal transplantation to prevent recurrence of disease in the allograft.[70][71][73][74]

secondary HUS: not due to Streptococcus pneumoniae

1st line – consider eculizumab or plasma exchange

Back
ACUTE
|
secondary HUS: not due to Streptococcus pneumoniae
1st line – 

consider eculizumab or plasma exchange

Treatment options in this setting are not well studied.

There are reports for the use of eculizumab and plasma infusions, but randomized controlled studies are not available. The prognosis in this setting is guarded.

If HUS is secondary to medications, those medications should be discontinued.

Plus – red cell transfusion

Back
ACUTE
|
secondary HUS: not due to Streptococcus pneumoniae
|
with anemia
Plus – 

red cell transfusion

Treatment recommended for ALL patients in selected patient group

Red cell transfusions should be given (as per guidelines) to ameliorate cardiovascular or respiratory symptoms or for severe anemia (hematocrit <18%).

Close attention should be paid to electrolytes, as a blood transfusion in the setting of active hemolysis and renal injury can result in severe and life-threatening hyperkalemia.

Plus – antihypertensives

Back
ACUTE
|
secondary HUS: not due to Streptococcus pneumoniae
|
with hypertension
Plus – 

antihypertensives

Treatment recommended for ALL patients in selected patient group

Hypertension can occur secondary to increased intravascular volume, electrolyte abnormalities, and underlying thrombotic microangiopathy affecting the kidney.

Blood pressure should be controlled to avoid renal damage and posterior reversible encephalopathy syndrome.

Recommended agents include calcium-channel blockers, vasodilators, and beta-blockers.

ACE inhibitors are not generally recommended in the acute setting, because of concerns of decreased renal perfusion, but can be used once the acute phase of HUS has subsided to help preserve renal function.[54][55]

Plus – dialysis

Back
ACUTE
|
secondary HUS: not due to Streptococcus pneumoniae
|
with acute kidney injury
Plus – 

dialysis

Treatment recommended for ALL patients in selected patient group

Dialysis is performed if clinically indicated: volume overload, oligoanuria, signs and symptoms of uremia, hyperkalemia, persistent severe acidosis (bicarbonate <10), hypertension secondary to volume overload that cannot be controlled with medical therapy, and necessity for transfusion in patients with volume overload and/or oliguria.[9]

Different modalities of dialysis are used including peritoneal dialysis, hemodialysis, and continuous veno-venous hemofiltration. The choice of modality varies depending on patient condition, institutional policy, and physician's discretion.

Plus – renal transplant

Back
ACUTE
|
secondary HUS: not due to Streptococcus pneumoniae
|
with irreversible acute kidney injury
Plus – 

renal transplant

Treatment recommended for ALL patients in selected patient group

For patients who have developed irreversible acute kidney injury, renal transplant can be considered.

Eculizumab may be required post renal transplantation to prevent recurrence of disease in the allograft.[70][71][73][74]

Renal transplant may not be viable for patients with comorbidities, such as cancer that is not in remission.

secondary HUS: due to S pneumoniae

1st line – antibiotic therapy

Back
ACUTE
|
secondary HUS: due to S pneumoniae
1st line – 

antibiotic therapy

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

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.[14]

Plus – red cell transfusion

Back
ACUTE
|
secondary HUS: due to S pneumoniae
|
with anemia
Plus – 

red cell transfusion

Treatment recommended for ALL patients in selected patient group

Red cell transfusions should be given (as per guidelines) to ameliorate cardiovascular or respiratory symptoms or for severe anemia (hematocrit <18%).

Washed red cells should be given to patients with Streptococcus pneumoniae-associated HUS.

Close attention should be paid to electrolytes, as a blood transfusion in the setting of active hemolysis and renal injury can result in severe and life-threatening hyperkalemia.

Plus – antihypertensives

Back
ACUTE
|
secondary HUS: due to S pneumoniae
|
with hypertension
Plus – 

antihypertensives

Treatment recommended for ALL patients in selected patient group

Hypertension can occur secondary to increased intravascular volume, electrolyte abnormalities, and underlying thrombotic microangiopathy affecting the kidney.

Blood pressure should be controlled to avoid renal damage and posterior reversible encephalopathy syndrome.

Recommended agents include calcium-channel blockers, vasodilators, and beta-blockers.

ACE inhibitors are not generally recommended in the acute setting, because of concerns of decreased renal perfusion, but can be used once the acute phase of HUS has subsided to help preserve renal function.[54][55]

Plus – dialysis

Back
ACUTE
|
secondary HUS: due to S pneumoniae
|
with acute kidney injury
Plus – 

dialysis

Treatment recommended for ALL patients in selected patient group

Dialysis is performed if clinically indicated: volume overload, oligoanuria, signs and symptoms of uremia, hyperkalemia, persistent severe acidosis (bicarbonate <10), hypertension secondary to volume overload that cannot be controlled with medical therapy, and necessity for transfusion in patients with volume overload and/or oliguria.[9]

Different modalities of dialysis are used including peritoneal dialysis, hemodialysis, and continuous veno-venous hemofiltration. The choice of modality varies depending on patient condition, institutional policy, and physician's discretion.

Plus – renal transplant

Back
ACUTE
|
secondary HUS: due to S pneumoniae
|
with irreversible acute kidney injury
Plus – 

renal transplant

Treatment recommended for ALL patients in selected patient group

For patients who have developed irreversible acute kidney injury, renal transplant can be considered.[46]

Renal transplant may not be viable for patients with comorbidities, such as cancer that is not in remission.

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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