Thrombotic microangiopathy and associated renal disorders
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Open Access
- 1 July 2012
- journal article
- research article
- Published by Oxford University Press (OUP) in Nephrology Dialysis Transplantation
- Vol. 27 (7), 2673-2685
- https://doi.org/10.1093/ndt/gfs279
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.Keywords
This publication has 176 references indexed in Scilit:
- Eculizumab as rescue therapy for atypical hemolytic uremic syndrome with normal platelet countPediatric Nephrology, 2012
- Common genetic variants in complement genes other than CFH, CD46 and the CFHRs are not associated with aHUSMolecular Immunology, 2011
- Systemic infections mimicking thrombotic thrombocytopenic purpuraAmerican Journal of Hematology, 2011
- The Role of Endothelial Cell Injury in Thrombotic MicroangiopathyAmerican Journal of Kidney Diseases, 2010
- aHUS caused by complement dysregulation: new therapies on the horizonPediatric Nephrology, 2010
- Genetics and complement in atypical HUSPediatric Nephrology, 2010
- Pathophysiology of thrombotic thrombocytopenic purpuraInternational Journal of Hematology, 2010
- Thrombomodulin Mutations in Atypical Hemolytic–Uremic SyndromeThe New England Journal of Medicine, 2009
- Plasma therapy in atypical haemolytic uremic syndrome: lessons from a family with a factor H mutationPediatric Nephrology, 2008
- VEGF Inhibition and Renal Thrombotic MicroangiopathyThe New England Journal of Medicine, 2008