Pediatric Hemolytic Uremic Syndrome Medication

Updated: Nov 12, 2018
  • Author: Robert S Gillespie, MD, MPH; Chief Editor: Craig B Langman, MD  more...
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Medication

Medication Summary

Supportive care remains the mainstay of therapy for Shiga toxin–producing E coli hemolytic-uremic syndrome (STEC-HUS) and is very important in atypical hemolytic-uremic syndrome (aHUS) as well. Medications such as antihypertensives, diuretics, anticonvulsants, and analgesics are indicated to treat specific symptoms or complications of hemolytic-uremic syndrome. These medications are have not clearly been demonstrated to alter the disease process.

Eculizumab is the first treatment approved by the US Food and Drug Administration (FDA) in September 2011 for adults and children with aHUS. [41] In a prospective trial of eculizumab in children and adolescents with atypical hemolytic uremic syndrome, Greenbaum et al reported that of 22 patients (5 months–17 years of age) followed for 26 weeks, all were able to discontinue plasma exchange/infusion, and 9 of the 11 patients who required dialysis at baseline discontinued and none initiated new dialysis. The study also reported that 16 patients had 25% or better improvement in serum creatinine and concluded that eculizumab was well tolerated; no deaths or meningococcal infections occurred. [42]

Unfortunately, several other agents that in theory should ameliorate hemolytic-uremic syndrome have failed to do so in clinical trials. These include thrombolytic agents (eg, heparin, urokinase), platelet inhibitors (eg, aspirin, dipyridamole), and a Shiga toxin (Stx)–binding agent (ie, Synsorb-Pk). Current evidence does not support use of these medications.

Corticosteroids are not useful in STEC-HUS. They may be of value in aHUS if the patient has an autoimmune-produced inhibitor of ADAMTS13. Clinical testing for inhibitors is available but has a long turnaround time.

Limited case reports describe using intravenous immune globulin (IVIG) in patients with aHUS associated with organ transplantation. IVIG does not have a role in hereditary aHUS nor in STEC-HUS.

Plasma therapies and eculizumab are covered in Treatment. They are indicated only for treatment of aHUS, or possibly STEC-HUS with associated CNS involvement, but plasma therapies have generally been superseded by treatment with eculizumab.

Studies have shown that antibiotics given to patients with diarrhea due to E coli 0157:H7 increase the risk of developing hemolytic-uremic syndrome. [43] A theory proposed to explain this finding is that antibiotic therapy causes rapid large-scale bacterial lysis with massive release of Stx, overwhelming host defense mechanisms. Whether antibiotics affect the course of established hemolytic-uremic syndrome remains unknown. Patients with E coli 0157 colitis usually clear the infection spontaneously.

Most pediatric nephrologists do not routinely use antibiotics in patients with STEC-HUS, based on a theoretical concern it could exacerbate the disease process. [44] However, antibiotics should be used when indicated according to clinical judgment. Examples include patients having suspected or documented bacteremia, urinary tract infection, or sepsis.

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Monoclonal Antibodies, Endocrine

Class Summary

Eculizumab is a monoclonal antibody indicated for atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy; effectiveness is based on the effects on thrombotic microangiopathy and renal function. It is not approved for patients with Shiga toxin–producing E coli hemolytic uremic syndrome (STEC-HUS).

Eculizumab (Soliris)

Eculizumab is a monoclonal blocking antibody to complement protein C5; it inhibits cleavage to C5a and C5b, thus preventing terminal complement complex C5b-9, thereby preventing RBC hemolysis. It inhibits terminal complement-mediated intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria and complement-mediated thrombotic microangiopathy in patients with aHUS.

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