Atypical hemolytic uremic syndrome in the setting of complement-amplifying conditions: case reports and a review of the evidence for treatment with eculizumab

Arif Asif, Ali Nayer, Christian S. Haas

Research output: Contribution to journalReview article

30 Citations (Scopus)

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, progressive, life-threatening form of thrombotic microangiopathy (TMA) predominantly caused by dysregulation of the alternative pathway of the complement system. Complement-amplifying conditions (CACs), including pregnancy complications [preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome], malignant hypertension, autoimmune diseases, transplantation, and others, are associated with the onset of TMA in up to 69 % of cases of aHUS. CACs activate the alternative pathway of complement and may be comorbid with aHUS or may unmask a previously undiagnosed case. In this review, three case reports are presented illustrating the onset and diagnosis of aHUS in the setting of different CACs (pregnancy complications, malignant hypertension, renal transplantation). The report also reviews the evidence for a variety of CACs, including those mentioned above as well as infections and drug-induced TMA, and the overlap with aHUS. Finally, we introduce an algorithm for diagnosis and treatment of aHUS in the setting of CACs. If TMA persists despite initial management for the specific CAC, aHUS should be considered. The terminal complement inhibitor eculizumab should be initiated for all patients with confirmed diagnosis of aHUS, with or without a comorbid CAC.

Original languageEnglish (US)
Pages (from-to)347-362
Number of pages16
JournalJournal of Nephrology
Volume30
Issue number3
DOIs
StatePublished - Jun 1 2017

Fingerprint

Thrombotic Microangiopathies
Malignant Hypertension
Alternative Complement Pathway
Pregnancy Complications
Complement Inactivating Agents
Therapeutics
Atypical Hemolytic Uremic Syndrome
eculizumab
Hemolysis
Pre-Eclampsia
Platelet Count
Kidney Transplantation
Autoimmune Diseases
Transplantation
Liver
Enzymes
Infection
Pharmaceutical Preparations

Keywords

  • Complement
  • Hypertension
  • Kidney transplantation
  • Pregnancy
  • Thrombotic microangiopathy

ASJC Scopus subject areas

  • Nephrology

Cite this

Atypical hemolytic uremic syndrome in the setting of complement-amplifying conditions : case reports and a review of the evidence for treatment with eculizumab. / Asif, Arif; Nayer, Ali; Haas, Christian S.

In: Journal of Nephrology, Vol. 30, No. 3, 01.06.2017, p. 347-362.

Research output: Contribution to journalReview article

@article{07da6be34984411084776002124319ff,
title = "Atypical hemolytic uremic syndrome in the setting of complement-amplifying conditions: case reports and a review of the evidence for treatment with eculizumab",
abstract = "Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, progressive, life-threatening form of thrombotic microangiopathy (TMA) predominantly caused by dysregulation of the alternative pathway of the complement system. Complement-amplifying conditions (CACs), including pregnancy complications [preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome], malignant hypertension, autoimmune diseases, transplantation, and others, are associated with the onset of TMA in up to 69 {\%} of cases of aHUS. CACs activate the alternative pathway of complement and may be comorbid with aHUS or may unmask a previously undiagnosed case. In this review, three case reports are presented illustrating the onset and diagnosis of aHUS in the setting of different CACs (pregnancy complications, malignant hypertension, renal transplantation). The report also reviews the evidence for a variety of CACs, including those mentioned above as well as infections and drug-induced TMA, and the overlap with aHUS. Finally, we introduce an algorithm for diagnosis and treatment of aHUS in the setting of CACs. If TMA persists despite initial management for the specific CAC, aHUS should be considered. The terminal complement inhibitor eculizumab should be initiated for all patients with confirmed diagnosis of aHUS, with or without a comorbid CAC.",
keywords = "Complement, Hypertension, Kidney transplantation, Pregnancy, Thrombotic microangiopathy",
author = "Arif Asif and Ali Nayer and Haas, {Christian S.}",
year = "2017",
month = "6",
day = "1",
doi = "10.1007/s40620-016-0357-7",
language = "English (US)",
volume = "30",
pages = "347--362",
journal = "Journal of Nephrology",
issn = "1121-8428",
publisher = "Wichtig Publishing",
number = "3",

}

TY - JOUR

T1 - Atypical hemolytic uremic syndrome in the setting of complement-amplifying conditions

T2 - case reports and a review of the evidence for treatment with eculizumab

AU - Asif, Arif

AU - Nayer, Ali

AU - Haas, Christian S.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, progressive, life-threatening form of thrombotic microangiopathy (TMA) predominantly caused by dysregulation of the alternative pathway of the complement system. Complement-amplifying conditions (CACs), including pregnancy complications [preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome], malignant hypertension, autoimmune diseases, transplantation, and others, are associated with the onset of TMA in up to 69 % of cases of aHUS. CACs activate the alternative pathway of complement and may be comorbid with aHUS or may unmask a previously undiagnosed case. In this review, three case reports are presented illustrating the onset and diagnosis of aHUS in the setting of different CACs (pregnancy complications, malignant hypertension, renal transplantation). The report also reviews the evidence for a variety of CACs, including those mentioned above as well as infections and drug-induced TMA, and the overlap with aHUS. Finally, we introduce an algorithm for diagnosis and treatment of aHUS in the setting of CACs. If TMA persists despite initial management for the specific CAC, aHUS should be considered. The terminal complement inhibitor eculizumab should be initiated for all patients with confirmed diagnosis of aHUS, with or without a comorbid CAC.

AB - Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, progressive, life-threatening form of thrombotic microangiopathy (TMA) predominantly caused by dysregulation of the alternative pathway of the complement system. Complement-amplifying conditions (CACs), including pregnancy complications [preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome], malignant hypertension, autoimmune diseases, transplantation, and others, are associated with the onset of TMA in up to 69 % of cases of aHUS. CACs activate the alternative pathway of complement and may be comorbid with aHUS or may unmask a previously undiagnosed case. In this review, three case reports are presented illustrating the onset and diagnosis of aHUS in the setting of different CACs (pregnancy complications, malignant hypertension, renal transplantation). The report also reviews the evidence for a variety of CACs, including those mentioned above as well as infections and drug-induced TMA, and the overlap with aHUS. Finally, we introduce an algorithm for diagnosis and treatment of aHUS in the setting of CACs. If TMA persists despite initial management for the specific CAC, aHUS should be considered. The terminal complement inhibitor eculizumab should be initiated for all patients with confirmed diagnosis of aHUS, with or without a comorbid CAC.

KW - Complement

KW - Hypertension

KW - Kidney transplantation

KW - Pregnancy

KW - Thrombotic microangiopathy

UR - http://www.scopus.com/inward/record.url?scp=85019638219&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019638219&partnerID=8YFLogxK

U2 - 10.1007/s40620-016-0357-7

DO - 10.1007/s40620-016-0357-7

M3 - Review article

C2 - 27848226

AN - SCOPUS:85019638219

VL - 30

SP - 347

EP - 362

JO - Journal of Nephrology

JF - Journal of Nephrology

SN - 1121-8428

IS - 3

ER -