Hemolytic-Uremic Syndrome Treatment & Management

Updated: Nov 16, 2017
  • Author: Malvinder S Parmar, MBBS, MS, FRCPC, FACP, FASN; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
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Treatment

Medical Care

Specific treatments for Shiga toxin–associated hemolytic-uremia syndrome (Stx-HUS) have not proven of value. Instead, comprehensive supportive therapy is still the mainstay during the acute phase.

There is no clear consensus on the use of antibiotics. The evidence avoidance of antibiotics unless patient is septic. An 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. [22] 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 Escherichia coli O157:H7 viability remained high.

Renal transplantation is safe and effective for children who progress to end-stage renal disease (ESRD). The recurrence rate in patients who undergo renal transplantation for HUS is 0-10%.

The U.S. Food and Drug Administration (FDA) has approved the use of eculizumab for the treatmant of atypical hemolytic uremic syndrome. This monoclonal antibody inhibits complement-mediated thrombotic microangiopathy.

Other treatments during the acute phase of the disease, including plasma therapy and use of intravenously infused immunoglobulin (IgG), fibrinolytic agents, antiplatelet agents, corticosteroids, and antioxidants have proved ineffective in controlled clinical trials. [23] Plasma exchange is not recommended as initial therapy in typical HUS.

Non–Styx-associated HUS

Plasma exchange is the initial treatment of choice in all adult patients with non-Stx-HUS (atypical HUS) or thrombotic thrombocytopenic purpura (TTP) and should be considered as early as possible in the disease course. The remarkable decline in mortality with the use of therapeutic plasma exchange has changed this fatal disease to a mostly curable illness. At present, the findings of unexplained thrombocytopenia and microangiopathic hemolytic anemia are sufficient to consider thrombotic microangiopathy and initiate plasma exchange.

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 impairment or heart failure.

Plasma treatment should be started within 24 hours of the patient's presentation, to decrease treatment failures. It should be continued once or twice a day for at least 2 days after complete remission.

Plasma therapy is contraindicated in Streptococcus 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. [16]

Eculizumab

Eculizumab (Soliris) is the only agent approved for the treatment of non–Stx-HUS. The FDA approved eculizumab for the treatment of non–Stx-HUS in 2011. Eculizumab is a humanized monoclonal antibody against C5 that inhibits the activation of terminal components of complement.

The safety and effectiveness of eculizumab in non–Stx-HUS were established in two single-arm trials in 37 adults and adolescents and one retrospective study in 19 pediatric and 11 adult patients. In those studies, eculizumab treatment led to improvement in kidney function, including elimination of the need for dialysis in several cases that had not responded plasma therapy. Patients treated with eculizumab also exhibited improvement in platelet counts and other blood parameters. [24]

Prospective phase II trials by Legendre and colleagues in 37 patients with non–Stx-HUS who were 12 years of age or older demonstrated that a shorter interval between the clinical manifestation of the disease and the initiation of treatment) was associated with significantly greater improvement in the estimated glomerular filtration rate. Legendre and colleagues concluded that, “the data highlight the inadequate efficacy of management with plasma exchange or infusion and confirm the clinically relevant treatment effect of eculizumab.” [25]

In a prospective phase III trial by this group in 41 patients with non–Stx-HUS who were 18 years of age or older, 30 patients had complete response of thrombotic microangiopathy, with normalization of the platelet count and lactate dehydrogenase (LDH) level and, and preservation of kidney function. Other benefits included improved quality of life, discontinuation of dialysis, and transplant protection. [26]

In the first prospective trial of eculizumab in pediatric non–Stx-HUS, Greenbaum et al reported that of  22 patients (5 months–17 years of age) 14 achieved a complete thrombotic microangiopathy response, 18 achieved hematologic normalization, and 16 had 25% or better improvement in serum creatinine. All patients were able to discontinue plasma exchange/infusion, and 9 of the 11 patients who required dialysis at baseline discontinued; none initiated new dialysis. Eculizumab was well tolerated; no deaths or meningococcal infections occurred. [27]

Transplantation

Renal transplantation 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, however, 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.

In patients with HF1 genetic defect, liver transplantation was thought to correct the defect, because HF1 is a plasma protein of hepatic origin. However, simultaneous liver and kidney transplantation in two children was 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

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 (20-40% of patients have seizures)
  • Control azotemia
  • Optimize nutrition
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Consultations

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

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

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.

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