What does atypical HUS treatment look like?

When aHUS is first diagnosed and symptoms can be sudden and severe, the primary goal of treatment is to stabilize the patient and stop further damage to the organs. [1]

Following stabilization of symptoms, maintenance treatment is continued to help the patient recover and to improve organ function as much as possible. [1,2]

There are various aHUS treatment options, including:

Plasma exchange

Plasma therapy has historically been the first line therapy and standard of care for aHUS. [1,2] This can be in the form of plasma exchange or plasma infusion. [2] In plasma exchange, the patient’s blood, which contains proteins that can lead to blood vessel damage and blood clot formation, is cleaned to remove those proteins and infused back into the patient. [1,2] In plasma infusion, plasma from healthy donors is infused into the patient to provide normal protein levels to the body. [1,3]

Plasma therapy is widely available throughout the world, including in low- and middle-income countries. [2] It is typically used when symptoms are sudden and severe in order to prevent injury to the patient as much as possible. [1,2]

Plasma therapy may not provide enough benefits to the patient and may not prevent the progression of organ damage, in addition to having potential side effects such as transfusion reactions and infection. [2] Because of these reasons, alternative treatments (complement inhibitors) are preferred over plasma therapy and have become the standard of care where available. [2]

Complement inhibitors

Complement inhibitors are a class of targeted drugs that block parts of the complement system. [2] Through this blocking, these medicines can prevent the damage caused by the overactivation of the complement system that drives aHUS. [2,3]

Complement inhibitors have become the treatment of choice for patients with aHUS. [2] Their use has led to a significant reduction in the number of aHUS patients undergoing dialysis as well as an increase in the number of patients with working kidneys. [4] Compared to plasma therapy, they control aHUS at a higher rate and have fewer risks. [2]

Even though complement inhibitors have substantially improved atypical HUS prognosis and patient survival and outcome, they are not available in every country and lead to an increased risk of meningitis (an infection that affects the area surrounding the brain and spinal cord). [5]

a kidney transplant

In patients with significant kidney injury or kidney failure, a kidney transplant, in which the patient undergoes surgery to replace the damaged kidney with a healthy donor kidney, may be necessary. [3] But as aHUS often reoccurs, the risk of damage to the new kidney is high. [3] Treatment with complement inhibitors has been shown to prevent aHUS recurrence in patients who have received a kidney transplant. [6]

In addition to these treatments for aHUS, patients may be given supportive treatments for their kidneys and to help with symptoms throughout the body. [2] These can include:

Blood transfusion


Blood transfusion, in which blood from a healthy donor is given to the patient, may be necessary for patients with low red blood cell numbers in the body. [2]

Fluid


Fluid and electrolyte (minerals in the body that carry an electric charge) management is important to help treat the symptoms of aHUS and prevent organ failure and kidney injury. [2]

high blood pressure


aHUS can lead to high blood pressure. Medication to lower high blood pressure may be needed for some patients. [2]

Dialysis


Dialysis, in which the patient’s blood is filtered by a machine to remove waste products and excess fluid, may be needed in case of kidney injury or failure. [2,7]

Studies have shown that, if a patient has recovered and no longer shows symptoms of the disease, treatment may be stopped in some cases, but regular monitoring is required to catch any signs of recurrence early. [2,8] The right amount of time to be on treatment remains unclear, and multiple studies have looked at the risk of aHUS relapse after stopping treatment. [2,8,9]

The decision for how long to continue treatment should be made by the doctor together with the patient, and a number of different factors have to be considered, including the patient’s genetic testing results and level of kidney damage. [9]

How is aHUS treatment generally organized?

Treatment and care of aHUS is complex. [10] Because patients can experience a wide range of symptoms and multiple organs may be affected, the treatment team is ideally made up of doctors and specialists from different areas of expertise. [10]

While the organization of treatment can vary for each patient and depends on the hospital or institution where the patient is receiving care, nephrologists (doctors specializing in care of the kidneys) and hematologists (doctors specializing in blood-related conditions) most often oversee aHUS treatment. [10] Patients may also be seen by critical care doctors for severe symptoms, as well as specialists in other organs that may be affected by the disease (such as the brain, heart, and lungs). [3,10]

It is recommended that the following are checked regularly in aHUS patients [11]:

  • Blood tests
  • Blood and urine tests for kidney function
  • Blood pressure
  • Signs and symptoms of infection


Ultimately, aHUS care is effective when general recommendations are personalized for each patient together with the treatment team. [11]

References

  1. Cataland SR, Wu HM. How I treat: the clinical differentiation and initial treatment of adult patients with atypical hemolytic uremic syndrome. Blood. 2014;123(16):2478-2484.
  2. Raina R, Krishnappa V, Blaha T, et al. Atypical Hemolytic-Uremic Syndrome: An Update on Pathophysiology, Diagnosis, and Treatment. Ther Apher Dial. 2019;23(1):4-21.
  3. Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 2011;6:60.
  4. Werion A, Rondeau E. Application of C5 inhibitors in glomerular diseases in 2021. Kidney Res Clin Pract. 2022;41(4):412-421.
  5. Ariceta G. Optimal duration of treatment with eculizumab in atypical hemolytic uremic syndrome (aHUS)-a question to be addressed in a scientific way. Pediatr Nephrol. 2019;34(5):943-949.
  6. Duineveld C, Glover EK, Bouwmeester RN, et al. Kidney Transplantation in Patients With aHUS: A Comparison of Eculizumab Prophylaxis Versus Rescue Therapy. Transplantation. 2024. Online ahead of print.
  7. Kaplan BS, Ruebner RL, Spinale JM, et al. Current treatment of atypical hemolytic uremic syndrome. Intractable Rare Dis Res. 2014;3(2):34-45.
  8. Ariceta G, Fakhouri F, Sartz L, et al. Eculizumab discontinuation in atypical haemolytic uraemic syndrome: TMA recurrence risk and renal outcomes. Clin Kidney J. 2021;14(9):2075-2084.
  9. Fakhouri F, Fila M, Hummel A, et al. Eculizumab discontinuation in children and adults with atypical hemolytic-uremic syndrome: a prospective multicenter study. Blood. 2021;137(18):2438-2449.
  10. Burke L, Sethi SK, Boyer O, et al. Voice of a caregiver: call for action for multidisciplinary teams in the care for children with atypical hemolytic uremic syndrome. Pediatr Nephrol. 2024;39(7):1961-1963.
  11. Ávila A, Cao M, Espinosa M, et al. Recommendations for the individualised management of atypical hemolytic uremic syndrome in adults. Front Med (Lausanne). 2023:10:1264310.