What is Atypical Hemolytic Uremic Syndrome:
Atypical Hemolytic Uremic Syndrome (aHUS) is a rare and complex kidney disorder that affects both children and adults. It is characterized by the triad of microangiopathic hemolytic anemia, thrombocytopenia (low platelet count), and acute kidney injury. Unlike the more common form of Hemolytic Uremic Syndrome (HUS), which is often associated with gastrointestinal infections, Atypical Hemolytic Uremic Syndrome typically occurs spontaneously and is primarily driven by dysregulation of the complement system, a part of the immune system responsible for protecting the body against pathogens.(1)
Understanding the Complexities of Atypical Hemolytic Uremic Syndrome:
Atypical Hemolytic Uremic Syndrome is a complex and multifactorial disease with various underlying causes. The dysregulation of the complement system plays a crucial role in the development of the condition. In Atypical Hemolytic Uremic Syndrome, the complement system becomes overactive or uncontrolled, leading to the formation of blood clots within small blood vessels throughout the body, including the kidneys. This process can result in damage to the kidney tissues and impaired kidney function.(2)
Genetic Factors Leading to the Development of Atypical Hemolytic Uremic Syndrome:
Genetic mutations are known to contribute significantly to the development of Atypical Hemolytic Uremic Syndrome. Research has identified mutations in genes encoding complement proteins, regulators, or components of the complement system in approximately 60-70% of Atypical Hemolytic Uremic Syndrome cases. These genetic abnormalities disrupt the delicate balance of the complement system, leading to uncontrolled activation and subsequent damage to the kidneys.
Acquired Factors That Can Trigger or Exacerbate Atypical Hemolytic Uremic Syndrome:
In addition to genetic predisposition, various acquired factors can trigger or exacerbate Atypical Hemolytic Uremic Syndrome. These include infections, medications, pregnancy, autoimmune diseases, and certain medical procedures. In some cases, the underlying cause of Atypical Hemolytic Uremic Syndrome may remain unidentified, which is referred to as idiopathic Atypical Hemolytic Uremic Syndrome.(3)
Clinical Presentation and Diagnosis of Atypical Hemolytic Uremic Syndrome:
The clinical presentation of Atypical Hemolytic Uremic Syndrome can vary widely among individuals, making diagnosis challenging. Symptoms often include fatigue, weakness, pale skin (due to anemia), decreased urine output, high blood pressure, and signs of kidney dysfunction. Laboratory tests revealing hemolytic anemia, low platelet count, and kidney injury are essential for the diagnosis of Atypical Hemolytic Uremic Syndrome. Further testing, including genetic analysis and complement pathway evaluation, may be required to confirm the diagnosis and determine the underlying cause.(4)
Treatment and Management of Atypical Hemolytic Uremic Syndrome:
The management of Atypical Hemolytic Uremic Syndrome requires a multidisciplinary approach involving nephrologists, hematologists, and other specialists. The primary goal of treatment is to prevent further damage to the kidneys and improve overall outcomes. The advent of targeted therapies, such as complement inhibitors, has revolutionized the treatment landscape for Atypical Hemolytic Uremic Syndrome. These medications, such as eculizumab, block the overactive complement pathway, helping to prevent further kidney damage and improve long-term renal function. Early initiation of treatment is crucial to minimize kidney injury and preserve kidney function.(5)
Atypical Hemolytic Uremic Syndrome is a rare kidney disorder with complex underlying mechanisms. Genetic mutations and dysregulation of the complement system contribute to the development of this condition. Prompt diagnosis and appropriate management, including the use of complement inhibitors, have significantly improved outcomes for patients with Atypical Hemolytic Uremic Syndrome. Further research and understanding of the disease’s intricacies are necessary to advance diagnostic techniques and develop more targeted therapies.
- Noris M, Remuzzi G. Atypical Hemolytic-Uremic Syndrome. N Engl J Med. 2009;361(17):1676-1687. doi:10.1056/NEJMra0902814
- 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. doi:10.2215/CJN.02230310
- Laurence J. Atypical Hemolytic Uremic Syndrome (aHUS): Making the Diagnosis. Clin Adv Hematol Oncol. 2012;10(11 Suppl 20):1-12.
- Dragon-Durey MA, Sethi SK, Bagga A, et al. Clinical features of anti-factor H autoantibody-associated hemolytic uremic syndrome. J Am Soc Nephrol. 2010;21(12):2180-2187. doi:10.1681/ASN.2010040376
- Loirat C, Fakhouri F, Ariceta G, et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2016;31(1):15-39. doi:10.1007/s00467-015-3076-7
- Licht C, Ardissino G, Ariceta G, et al. The global aHUS registry: methodology and initial patient characteristics. BMC Nephrol. 2015;16:207. doi:10.1186/s12882-015-0205-8
- Greenbaum LA, Fila M, Ardissino G, et al. Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int. 2016;89(3):701-711. doi:10.1016/j.kint.2015.11.033
- Campistol JM, Arias M, Ariceta G, et al. An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia. 2013;33(1):27-45. doi:10.3265/Nefrologia.pre2012.Oct.11622
- Goodship THJ, Cook HT, Fakhouri F, et al. Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy: Conclusions from a “Kidney Disease: Improving Global Outcomes” (KDIGO) Controversies Conference. Kidney Int. 2017;91(3):539-551. doi:10.1016/j.kint.2016.10.005
- Legendre CM, Licht C, Muus P, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013;368(23):2169-2181. doi:10.1056/NEJMoa1206319
- What is Hemolytic Uremic Syndrome?
- What is Hemolytic-Uremic Syndrome, Know its Causes, Symptoms, Treatment