Thrombotic microangiopathy and associated renal disorders
File(s)
Author(s)
Barbour, T
Johnson, S
Cohney, S
Hughes, P
Type
Journal Article
Abstract
Thrombotic microangiopathy (TMA) is a pathological process involving thrombocytopenia, microangiopathic haemolytic anaemia and microvascular occlusion. TMA is common to haemolytic uraemic syndrome (HUS) associated with shiga toxin or invasive pneumococcal infection, atypical HUS (aHUS), thrombotic thrombocytopenic purpura (TTP) and other disorders including malignant hypertension. HUS complicating infection with shiga toxin-producing Escherichia coli (STEC) is a significant cause of acute renal failure in children worldwide, occurring sporadically or in epidemics. Studies in aHUS have revealed genetic and acquired factors leading to dysregulation of the alternative complement pathway. TTP has been linked to reduced activity of the ADAMTS13 cleaving protease (typically with an autoantibody to ADAMTS13) with consequent disruption of von Willebrand factor multimer processing. However, the convergence of pathogenic pathways and clinical overlap create diagnostic uncertainty, especially at initial presentation. Furthermore, recent developments are challenging established management protocols. This review addresses the current understanding of molecular mechanisms underlying TMA, relating these to clinical presentation with an emphasis on renal manifestations. A diagnostic and therapeutic approach is presented, based on international guidelines, disease registries and published trials. Early treatment remains largely empirical, consisting of plasma replacement/exchange with the exception of childhood STEC-HUS or pneumococcal sepsis. Emerging therapies such as the complement C5 inhibitor eculizumab for aHUS and rituximab for TTP are discussed, as is renal transplantation for those patients who become dialysis-dependent as a result of aHUS.
Date Issued
2012-07-01
Date Acceptance
2012-04-07
Citation
Nephrology Dialysis Transplantation, 2012, 27 (7), pp.2673-2685
ISSN
1460-2385
Publisher
Oxford University Press (OUP)
Start Page
2673
End Page
2685
Journal / Book Title
Nephrology Dialysis Transplantation
Volume
27
Issue
7
Copyright Statement
© The Author 2012. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited
License URL
Subjects
Science & Technology
Life Sciences & Biomedicine
Transplantation
Urology & Nephrology
TRANSPLANTATION
UROLOGY & NEPHROLOGY
HUS
TTP
complement
kidney
eculizumab
HEMOLYTIC-UREMIC SYNDROME
COMPLEMENT-FACTOR-H
VON-WILLEBRAND-FACTOR
MEMBRANE COFACTOR PROTEIN
LIVER-KIDNEY TRANSPLANTATION
THROMBOCYTOPENIC PURPURA
PLASMA-EXCHANGE
FACTOR-I
ADAMTS13 ACTIVITY
ESCHERICHIA-COLI
Publication Status
Published