Atypical HemolyticUremic Syndrome: A Clinical Review

Ali Nayer, Arif Asif

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Atypical hemolyticuremic syndrome (HUS) is a rare life-threatening disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, and ischemic injury to organs, especially the kidneys. Microvascular injury and thrombosis are the dominant histologic findings. Complement activation through the alternative pathway plays a critical role in the pathogenesis of atypical HUS. Genetic abnormalities involving complement regulatory proteins and complement components form the molecular basis for complement activation. Endothelial cell dysfunction, probably because of the effects of complement activation, is an intermediate stage in the pathophysiologic cascade. Atypical HUS has a grave prognosis. Although mortality approaches 25% during the acute phase, end-stage renal disease develops in nearly half of patients within a year. Atypical HUS has a high recurrence rate after renal transplantation, and recurrent disease often leads to graft loss. Plasma therapy in the form of plasma exchange or infusion has remained the standard treatment for atypical HUS. However, many patients do not respond to plasma therapy and some require prolonged treatment. Approved by the Food and Drug Administration in the treatment of atypical HUS, eculizumab is a humanized monoclonal antibody that blocks cleavage of complement C5 into biologically active mediators of inflammation and cytolysis. Although case reports have shown the efficacy of eculizumab, randomized clinical trials are lacking. Therapeutic strategies targeting endothelial cells have demonstrated promising results in experimental settings. Therefore, inhibitors of angiotensin-converting enzyme, HMG-CoA reductase, and xanthine oxidase as well as antioxidants, such as ascorbic acid, may have salutary effects in patients with atypical HUS.

Original languageEnglish (US)
Pages (from-to)e151-e158
JournalAmerican Journal of Therapeutics
Volume23
Issue number1
DOIs
StatePublished - Jan 1 2016

Fingerprint

Complement Activation
Therapeutics
Endothelial Cells
Complement C5
Alternative Complement Pathway
Hydroxymethylglutaryl CoA Reductases
Antibodies, Monoclonal, Humanized
Inflammation Mediators
Plasma Exchange
Xanthine Oxidase
Hemolytic Anemia
Wounds and Injuries
United States Food and Drug Administration
Angiotensin-Converting Enzyme Inhibitors
Thrombocytopenia
Kidney Transplantation
Ascorbic Acid
Chronic Kidney Failure
Complement System Proteins
Thrombosis

Keywords

  • atypical hemolyticuremic syndrome
  • complements
  • eculizumab
  • endothelial cells
  • kidney

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Atypical HemolyticUremic Syndrome : A Clinical Review. / Nayer, Ali; Asif, Arif.

In: American Journal of Therapeutics, Vol. 23, No. 1, 01.01.2016, p. e151-e158.

Research output: Contribution to journalArticle

Nayer, Ali ; Asif, Arif. / Atypical HemolyticUremic Syndrome : A Clinical Review. In: American Journal of Therapeutics. 2016 ; Vol. 23, No. 1. pp. e151-e158.
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