Atypical Hemolytic Uremic Syndrome

What is atypical hemolytic uremic syndrome?

Atypical hemolytic uremic syndrome (atypical HUS or aHUS) is a rare type of blood disease in which the body’s smallest blood vessels are damaged. These blood vessels can be inside vital organs, like the kidneys, intestines, heart, and brain. [1,2]

In aHUS patients, tiny blood clots (also known as microthrombi) form in these small blood vessels and block blood flow to the organs, causing damage and even organ failure. [2] This blood vessel damage and blood clot formation is caused by overactivation of the body’s complement system. [2]

The complement system is a part of the body’s immune system and helps with defense against invading pathogens and with removing cellular debris and unhealthy cells. [3] When the complement system is overactivated and uncontrolled, it can cause disease. [3]

ultra-rare-disease

aHUS is an ultra-rare disease with <2 cases per million people diagnosed every year. There are an estimated 40,000 people worldwide living with aHUS. [4]

adults

Boys and girls are affected equally by aHUS, with 40-50% of patients seeing first signs of disease during childhood. [4,5] For adults, a greater number of patients are female. [6]

Kidneys

The kidneys are the key affected organ for patients with aHUS. [6] Without effective treatment, up to 50% of patients may lose the ability of the kidneys to function on their own. [7]

How does aHUS affect the kidneys?

aHUS affects the entire body and can cause a range of symptoms in various organs, including the kidneys. [2] When microthrombi form in the small blood vessels that filter the blood in the kidneys (also known as glomeruli), the ability of the kidneys to filter blood and produce urine is reduced. [2,8]

The most common signs of kidney injury in aHUS patients are [2]:

  • High levels of protein in the urine
  • Blood in the urine
  • High blood pressure
  • High levels of body waste products (such as urea and creatinine) in the blood

How are treated patients living with aHUS today?

There are treatment options available for aHUS. [9] These have led to encouraging results, with fewer patients needing lifelong dialysis (in which the patient’s blood is filtered by a machine to remove waste products and excess fluid) and more patients with healthy kidney function. [9] 

The Global aHUS Registry conducted a survey with aHUS patients to better understand the impact of aHUS on their daily lives. [10]

At the last follow-up, more than 75% of aHUS patients described their health status as “excellent”, “very good”, or “good”, 19.2% as “fair”, and 4.3% as “poor”. [10] Fatigue, headache, and weakness were the most common symptoms shared. [10]

Pie chart displaying ratings with percentages

Of the 511 patients surveyed, approximately 10% reported not working or not working full-time due to aHUS. [10] The remaining ~90% of patients described themselves as [10]:

  • Working a full-time job
  • Working a part-time job
  • Not working (unrelated to aHUS diagnosis)
  • Retired
  • Students
  • Other (made up mostly by homemakers, self-employed, and patients receiving disability payments)
     

Continue reading to learn more about aHUS and available treatment options.

Pie chart showing employment and activity status with percentages.

References

  1.  https://unckidneycenter.org/kidneyhealthlibrary/glomerular-disease/thrombotic-microangiopathy-tma/. Accessed May 2024.
  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. Ricklin D, Hajishengallis G, Yang K, et al. Complement: a key system for immune surveillance and homeostasis. Nat Immunol. 2010;11(9):785-797.
  4. Yan K, Desai K, Gullapalli L, et al. Epidemiology of Atypical Hemolytic Uremic Syndrome: A Systematic Literature Review. Clin Epidemiol. 2020;12:295-305.
  5. Fakhouri F, Loirat C. Anticomplement Treatment in Atypical and Typical Hemolytic Uremic Syndrome. Semin Hematol. 2018;55(3):150-158.
  6. Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 2011;6:60.
  7. Noris M, Caprioli J, Bresin E, et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol. 2010;5(10):1844-1859.
  8. Harris CL, Pouw RB, Kavanagh D, et al. Developments in anti-complement therapy; from disease to clinical trial. Mol Immunol. 2018;102:89-119.
  9. Werion A, Rondeau E. Application of C5 inhibitors in glomerular diseases in 2021. Kidney Res Clin Pract. 2022;41(4):412-421.
  10. Greenbaum LA, Licht C, Nikolaou V, et al. Functional Assessment of Fatigue and Other Patient-Reported Outcomes in Patients Enrolled in the Global aHUS Registry. Kidney Int Rep. 2020;5(8):1161-1171