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Hemolytic uremic syndrome

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Abstract

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy defined by thrombocytopenia, nonimmune microangiopathic hemolytic anemia, and acute renal failure. The most frequent form is associated with infections by Shiga-like toxin-producing bacteria (STEC-HUS). Rarer cases are triggered by neuraminidase-producing Streptococcus pneumoniae (pneumococcal-HUS). The designation of aHUS is used to refer to those cases in which an infection by Shiga-like toxin-producing bacteria or S. pneumoniae can be excluded. Studies performed in the last two decades have documented that hyperactivation of the complement system is the pathogenetic effector mechanism leading to the endothelial damage and the microvascular thrombosis in aHUS. Recent data suggested the involvement of the complement system in the pathogenesis of STEC-HUS and pneumococcal-HUS as well. Clinical signs and symptoms may overlap among the different forms of HUS; however, pneumococcal-HUS and aHUS have a worse prognosis compared with STEC-HUS. Early diagnosis and identification of underlying pathogenetic mechanism allows instating specific support measures and therapies. In clinical trials in patients with aHUS, complement inhibition by eculizumab administration leads to a rapid and sustained normalization of hematological parameters with improvement in long-term renal function. This review summarizes current concepts about the epidemiological findings, the pathological and clinical aspects of STEC-HUS, pneumococcal-HUS, and aHUS, and their diagnosis and management.

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Acknowledgments

This work has been partially supported by grants from Fondazione ART per la Ricerca sui Trapianti ONLUS (Milano Italy) and the European Community (FP7 Grant 2012-305608 EURenOmics). The authors wish to thank Dr. Claudio Tripodo (University of Palermo, Italy) for kindly providing the images of C3 and C9 staining in kidney biopsies from HUS patients.

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Authors and Affiliations

  1. IRCCS Istituto di Ricerche Farmacologiche “Mario Negri”, Clinical Research Center for Rare Diseases “Aldo e Cele Daccò”, Via Camozzi, 3, Ranica, Bergamo, 24020, Italy

    Caterina Mele, Giuseppe Remuzzi & Marina Noris

  2. Unit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy

    Giuseppe Remuzzi

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  1. Caterina Mele
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  2. Giuseppe Remuzzi
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  3. Marina Noris
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Correspondence to Marina Noris.

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This article is a contribution to the special issue on Immunopathology of Glomerular Diseases - Guest Editors: P. Ronco and J. Floege

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Mele, C., Remuzzi, G. & Noris, M. Hemolytic uremic syndrome. Semin Immunopathol 36, 399–420 (2014). https://doi.org/10.1007/s00281-014-0416-x

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