aHUS

(atypical Haemolytic Uremic Syndrome)

About aHUS

Atypical Haemolytic Uremic Syndrome (aHUS) is a systemic, progressive and potentially fatal disease.

It is caused by chronic, uncontrolled complement activation that leads to thrombotic microangiopathy (TMA) and severe terminal organ damage.1,2

The disease

aHUS is the result of a mutation in one or more complement-regulating genes, which leads to uncontrolled, excessive complement activation.4,5,6

In healthy individuals, complement works to defend against foreign particles and the system is regulated perfectly in order to prevent damage to organs and tissue. However, in patients with aHUS, the underlying gene mutations mean the complement cannot be controlled when it is activated.4

aHUS (atypical Haemolytic Uremic Syndrome) is caused by chronic, uncontrolled activation of complement, which is part of the body's immune system. This causes complement-mediated thrombotic microangiopathy (TMA), which is the formation of clots in small blood vessels throughout the body.1-4 TMA can lead to strokes, heart attacks, kidney failure and premature death.

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aHUS KDIGO

Watch this video to learn about the conclusions published by the Kidney Disease Improving Global Outcomes (KDIGO) organisation, including the diagnostic flowchart for thrombotic microangiopathy or TMA, and the best treatment options for these conditions.

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aHUS and pregnancy

The video discusses the significant risk of thrombotic microangiopathies (including thrombotic thrombocytopenic purpura and haemolytic uremic syndrome) during pregnancy and childbirth.

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TMA and aHUS

This video explains the differential diagnosis of TMA.3

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aHUS and kidney transplantation

This explains why an aHUS diagnosis is often associated with transplantations – a major risk factor for end-stage renal disease or death.1

Diagnosis

Conditions in which TMA occurs include Shiga toxin-induced haemolytic uremic syndrome (STEC-HUS), thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uremic syndrome (aHUS).1,7 aHUS is a rare, progressive and potentially fatal disease caused by chronic, uncontrolled activation of the alternative complement pathway.4,5 If left untreated, patients with aHUS are at risk for end-stage renal disease (ESRD), failures of other organs and premature death.4,6,8

Thrombotic microangiopathies (TMA) are a group of diseases characterised by thrombocytopenia, microangiopathic haemolytic anaemia and organ dysfunction. Ischaemic damage can occur in the brain, kidneys, heart, pancreas and lungs, among others.1,9 TMAs exhibit similar signs and symptoms, but are due to other causes.1,7

Campistol JM, Arias M., Ariceta G. et al. Update on Atypical Hemolytic Uremic Syndrome: diagnosis and treatment. Consensus document. Nefrología. 2015; 35(6): 421–447. 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):701–11. Laurence J., et al. Clin Adv Hematol Oncol. 2016, 14 (11 Zusatzblatt 11) 2–15. 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):1844–59. Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009;361(17):1676–87. Hofer J, Rosales A, Fischer C, et al. Extra-renal manifestations of complement-mediated thrombotic microangiopathies. Front Pediatr. 2014;2:97. Goodship TH, 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):539–51. Fremeaux-Bacchi V, Fakhouri F, Garnier A, et al. Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol. 2013;8(4):554–62. Loirat C, Fremeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 2011;6:60.