Hemolytic-Uremic Syndrome Treatment & Management

Treatments for Stx-HUS have not proven of value, and comprehensive supportive therapy is still the mainstay during the acute phase, as follows:

• Antibiotics: There is no clear consensus on the use of antibiotics and the evidence supports that antibiotics should be avoided unless patient is septic. A recent in-vitro study demonstrated that, although growth-inhibitory levels of antibiotics suppressed Stx production, subinhibitory levels of certain antibiotics that target DNA synthesis, including ciprofloxacin and trimethoprim-sulfamethoxazole, increased Stx production.^[13] Stx production did not increase with use of antibiotics that target the cell wall, transcription, or translation. In contrast, Stx levels were significantly reduced with azithromycin, even when O157:H7 viability remained high.
• Stx-binding agent: Oral administration of SYNSORB PK, which is composed of silicon particles linked to globotriaosylceramide, failed to provide a benefit over placebo.
• Renal transplantation: This procedure is safe and effective for children who progress to ESRD, with a recurrence rate of 0-10%.
• Other therapies: Other treatments, including plasma therapy and use of intravenously infused immunoglobulin (IgG), fibrinolytic agents, antiplatelet agents, corticosteroids, and antioxidants were ineffective in controlled clinical trials during the acute phase of the disease.

Treatment of non–Stx-HUS is as follows:

• Plasma manipulation, exchange versus infusion: The mortality rate decreased from 50% to 25% with the introduction of plasma manipulation, but its efficacy during the acute phase is debated. Plasma exchange might be more effective than infusion, as it removes potentially toxic substances from the circulation. Plasma exchange rather than infusion should be considered first-line therapy in situations that limit the amount of plasma that can be infused, such as renal or heart failure.
• Plasma treatment should be started within 24 hours of the patient's presentation to decrease treatment failures and then continued once or twice a day for at least 2 days after complete remission. Plasma therapy is contraindicated in S pneumoniae –induced non–Stx-HUS; it may exacerbate the disease because adult plasma contains antibodies against the Thomsen-Friedenreich antigen. A case was recently described showing efficacy of long-term, high-dose plasma infusion (30 mL/kg) at weekly intervals over 30 months, but the long-term effects are still unknown.^[12]
• Renal transplantation: This procedure is not an option for non–Stx-HUS because of the 50% recurrence rate and >90% rate of graft failure in patients with recurrence. Recurrence rates (30-100%) are significantly higher in patients with HF1 mutations than in those without this mutation. In patients with MCP mutation, outcomes are favorable, and renal transplantation may correct the local MCP dysfunction, as MCP is a membrane-bound protein that is highly expressed in the kidney.
• Liver transplantation: In patients with HF1 genetic defect, liver transplantation was thought to correct the defect, because HF1 is a plasma protein of liver origin. However, simultaneous liver and kidney transplantation in 2 children were complicated by premature liver failure. At present, this procedure should not be performed unless a patient is at imminent risk for life-threatening complications.

Supportive therapy is as follows:

• Maintain fluid and electrolyte balance.
• Adequate blood-pressure control and adequate renin-angiotensin blockade is helpful for patients who have chronic kidney disease after an episode of Stx-HUS.
• For seizure control, consider prophylactic phenytoin in patients with neurologic symptoms, as 20-40% of patients have seizures.
• Control azotemia.
• Optimize nutrition.

Some children with gastrointestinal involvement may require surgery and prolonged parenteral feeding.

Splenectomy is used as a last resort in refractory TTP; however, the basis for this treatment is unknown.

Patients with hemolytic-uremic syndrome (HUS) may require consultation with the following subspecialists:

• Nephrologist
• Hematologist
• Neurologist in cases of neurologic involvement
• Intensivists for intensive care unit (ICU) management

Provide nutritional support during the acute illness. If patients have severe diarrhea, they may require parenteral nutrition. Early restriction of proteins, in addition to renin-angiotensin blockade, may have a beneficial effect on the long-term renal outcome in patients who develop chronic kidney disease after Stx-HUS.