HUS - Hämolytisch Urämisches Syndrom

HUS - Hämolytisch Urämisches Syndrom

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Klassisches Hämolytisch Urämisches Syndrom (HUS)
Im Rahmen der HUS-Net Studie führen wir seit 1.1.1997 ein Register für Patienten mit klassischem D+HUS - Studie geschlossen -

Ziele dieser Studie sind:

Epidemiologische Erfassung der D+HUS Fälle mit Erkrankungsalter, Erreger und Serotypen der Stx+D+HUS Fälle
Klinische Manifestation der Erkrankung
Therapie des klassischen HUS
Follow-up zur Feststellung der Langzeitfolgen
Risikofaktoren für Langzeitkomplikationen
Etablierung eines umfassenden Evidenz-basierten Models zur HUS Pathogenese

Atypisches Hämolytisch Urämisches Syndrom (aHUS)
Die HUS-Net Studie untersucht sowohl die Genetik als auch die Beteiligung des Komplementsystems dieser schweren Nierenerkrankung. - Studie geschlossen -

Die Ziele dieser Studie sind:

Genetische Analyse von Patienten mit aHUS
Etablierung eines umfangreichen Evidenz-basierten Modells zur Ätiopathogenese des aHUS
Identifikation und Validierung genetischer & erworbener Risikofaktoren für aHUS
Differenzierung der verschiedenen Subgruppen dieser Erkrankung
Verbesserung der Therapie im Allgemeinen
Klinik und Verlauf des rekurrierenden aHUS
Erarbeitung eines Indikationsprofils für eine entsprechende individualisierte Therapie bei aHUS
Verbesserung der Therapie im Allgemeinen
Evaluierung einer rekurrenzfreien Transplantation bei aHUS Patienten mit Nierenersatztherapie

Publikationen:

Enterohemorrhagic hemolytic uremic syndrome (eHUS)

The structure of the Shiga toxin 2a A-subunit dictates the interactions of the toxin with blood components. Brigotti M, Orth-Höller D, Carnicelli D, Porcellini E, Galassi E, Tazzari PL, Ricci F, Manoli F, Manet I, Talasz H, Lindner HH, Speth C, Erbeznik T, Fuchs S, Posch W, Chatterjee S, Würzner R. Cell Microbiol. 2019 May;21(5):e13000.

Shiga toxin 2a binds antithrombin and heparin, but does not directly activate platelets. Knabl L, Berktold M, Hamad OA, Fromell K, Chatterjee S, Speth C, Talasz H, Lindner K, Hermann M, Nilsson-Ekdahl K, Nilsson B, Streif W, Martini J, Würzner R, Orth-Höller D. Int J Med Microbiol. 2018 Oct;308(7):969-976.

An update on the thrombotic microangiopathies hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Riedl M, Orth-Höller D, Würzner R. Semin Thromb Hemost. 2014 Jun;40(4):413-5.

Treatment of enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome (eHUS). Würzner R, Riedl M, Rosales A, Orth-Höller D. Semin Thromb Hemost. 2014 Jun;40(4):508-16.

Need for long-term follow-up in enterohemorrhagic Escherichia coli-associated hemolytic uremic syndrome due to late-emerging sequelae. Rosales A, Hofer J, Zimmerhackl LB, Jungraithmayr TC, Riedl M, Giner T, Strasak A, Orth-Höller D, Würzner R, Karch H; German-Austrian HUS Study Group. Clin Infect Dis. 2012 May;54(10):1413-21.

Enterohemorrhagic Escherichia coli O26:H11-Associated Hemolytic Uremic Syndrome: Bacteriology and Clinical Presentation.Zimmerhackl LB, Rosales A, Hofer J, Riedl M, Jungraithmayr T, Mellmann A, Bielaszewska M, Karch H. Semin Thromb Hemost. 2010 Sep;36(6):586-93. Epub 2010 Sep 23.

Shiga toxin activates complement and binds factor H: evidence for an active role of complement in hemolytic uremic syndrome. Orth D, Khan AB, Naim A, Grif K, Brockmeyer J, Karch H, Joannidis M, Clark SJ, Day AJ, Fidanzi S, Stoiber H, Dierich MP, Zimmerhackl LB, Würzner R. J Immunol. 2009 May 15;182(10):6394-400.

Sorbitol-fermenting Shiga toxin-producing Escherichia coli O157 in Austria. Orth D, Grif K, Zimmerhackl LB, Würzner R. Wien Klin Wochenschr. 2009;121(3-4):108-12.

Serine protease espP subtype alpha, but not beta or gamma, of Shiga toxin-producing Escherichia coli is associated with highly pathogenic serogroups. Khan AB, Naim A, Orth D, Grif K, Mohsin M, Prager R, Dierich MP, Würzner R. Int J Med Microbiol. 2009 Apr;299(4):247-54.

Prevention and treatment of enterohemorrhagic Escherichia coli infections in humans. Orth D, Grif K, Zimmerhackl LB, Würzner R. Expert Rev Anti Infect Ther. 2008 Feb;6(1):101-8.

Treatment and outcome of Shiga-toxin-associated hemolytic uremic syndrome (HUS). Scheiring J, Andreoli SP, Zimmerhackl LB.Pediatr Nephrol. 2008 Oct;23(10):1749-60.

The Shiga toxin genotype rather than the amount of Shiga toxin or the cytotoxicity of Shiga toxin in vitro correlates with the appearance of the hemolytic uremic syndrome. Orth D, Grif K, Khan AB, Naim A, Dierich MP, Würzner R. Diagn Microbiol Infect Dis. 2007 Nov;59(3):235-42.

What makes an enterohemorrhagic Escherichia coli? Orth D, Würzner R. Clin Infect Dis. 2006 Nov 1;43(9):1168-9.

Sorbitol-fermenting Shiga toxin-producing Escherichia coli O157: indications for an animal reservoir. Orth D, Grif K, Dierich MP, Würzner R. Epidemiol Infect. 2006 Aug;134(4):719-23.

Importance of environmental transmission in cases of EHEC O157 causing hemolytic uremic syndrome. Grif K, Orth D, Lederer I, Berghold C, Roedl S, Mache CJ, Dierich MP, Würzner R. Eur J Clin Microbiol Infect Dis. 2005 Apr;24(4):268-71.

Clinical course and the role of shiga toxin-producing Escherichia coli infection in the hemolytic-uremic syndrome in pediatric patients, 1997-2000, in Germany and Austria: a prospective study. Gerber A, Karch H, Allerberger F, Verweyen HM, Zimmerhackl LB.J Infect Dis. 2002 Aug 15;186(4):493-500.

Complement in enterohemorrhagic hemolytic uremic syndrome (eHUS)

Role of complement in enterohemorrhagic Escherichia coli-Induced hemolytic uremic syndrome. Orth-Höller D, Würzner R. Semin Thromb Hemost. 2014 Jun;40(4):503-7.

Interaction of Shiga toxin 2 with complement regulators of the factor H protein family. Poolpol K, Orth-Höller D, Speth C, Zipfel PF, Skerka C, de Córdoba SR, Brockmeyer J, Bielaszewska M, Würzner R. Mol Immunol. 2014 Mar;58(1):77-84.

Shiga toxin 2 reduces complement inhibitor CD59 expression on human renal tubular epithelial and glomerular endothelial cells. Ehrlenbach S, Rosales A, Posch W, Wilflingseder D, Hermann M, Brockmeyer J, Karch H, Satchell SC, Würzner R, Orth-Höller D. Infect Immun. 2013 Aug;81(8):2678-85.

Inhibition of terminal complement activation in severe Shiga toxin-associated HUS - perfect example for a fast track from bench to bedside. Orth-Höller D, Riedl M, Würzner R. EMBO Mol Med. 2011 Nov;3(11):617-9.

Complement in typical hemolytic uremic syndrome. Orth D, Würzner R.Semin Thromb Hemost. 2010 Sep;36(6):620-4.

EspP, a serine protease of enterohemorrhagic Escherichia coli, impairs complement activation by cleaving complement factors C3/C3b and C5. Orth D, Ehrlenbach S, Brockmeyer J, Khan AB, Huber G, Karch H, Sarg B, Lindner H, Würzner R. Infect Immun. 2010 Oct;78(10):4294-301.

Atypical hemolytic uremic syndrome

Novel biomarker and easy to perform ELISA for monitoring complement inhibition in patients with atypical hemolytic uremic syndrome treated with eculizumab. Riedl M, Hofer J, Giner T, Rosales A, Häffner K, Simonetti GD, Walden U, Maier T, Heininger D, Jeller V, Weiss G, van den Heuvel L, Zimmerhackl LB, Würzner R, Jungraithmayr TC. J Immunol Methods. 2016 Aug;435:60-7.

An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Loirat C, Fakhouri F, Ariceta G, Besbas N, Bitzan M, Bjerre A, Coppo R, Emma F, Johnson S, Karpman D, Landau D, Langman CB, Lapeyraque AL, Licht C, Nester C, Pecoraro C, Riedl M, van de Kar NC, Van de Walle J, Vivarelli M, Frémeaux-Bacchi V; HUS International. Pediatr Nephrol. 2016 Jan;31(1):15-39.

Spectrum of complement-mediated thrombotic microangiopathies: pathogenetic insights identifying novel treatment approaches. Riedl M, Fakhouri F, Le Quintrec M, Noone DG, Jungraithmayr TC, Fremeaux-Bacchi V, Licht C. Semin Thromb Hemost. 2014 Jun;40(4):444-64.

Thrombotic microangiopathy: atypical HUS: current diagnostic and therapeutic approaches. Rosales A, Riedl M, Zimmerhackl LB. Nat Rev Nephrol. 2010 Sep;6(9):504-6.

Prophylactic eculizumab after renal transplantation in atypical hemolytic-uremic syndrome. Zimmerhackl LB, Hofer J, Cortina G, Mark W, Würzner R, Jungraithmayr TC, Khursigara G, Kliche KO, Radauer W. N Engl J Med. 2010 May 6;362(18):1746-8

Complement regulation disorders and outcome after transplantation in children with atypical hemolytic uremic syndrome. Rosales A, Hofer J, Zimmerhackl LBSalud I Ciencia 2010;17:320-324.

Clinical practice. Today's understanding of the haemolytic uraemic syndrome. Scheiring J, Rosales A, Zimmerhackl LB. Eur J Pediatr. 2010 Jan;169(1):7-13. Epub 2009 Aug 26.

A large family with a gain-of-function mutation of complement C3 predisposing to atypical hemolytic uremic syndrome, microhematuria, hypertension and chronic renal failure. Lhotta K, Janecke AR, Scheiring J, Petzlberger B, Giner T, Fally V, Würzner R, Zimmerhackl LB, Mayer G, Fremeaux-Bacchi V.Clin J Am Soc Nephrol. 2009 Aug;4(8):1356-62.

Eculizumab for atypical hemolytic-uremic syndrome. Nürnberger J, Philipp T, Witzke O, Opazo Saez A, Vester U, Baba HA, Kribben A, Zimmerhackl LB, Janecke AR, Nagel M, Kirschfink M. N Engl J Med. 2009 Jan 29;360(5):542-4.

Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Ariceta G, Besbas N, Johnson S, Karpman D, Landau D, Licht C, Loirat C, Pecoraro C, Taylor CM, Van de Kar N, Vandewalle J, Zimmerhackl LB; European Paediatric Study Group for HUS.Pediatr Nephrol. 2009 Apr;24(4):687-96.

Renal transplantation in HUS patients with disorders of complement regulation. Zimmerhackl LB, Scheiring J, Prüfer F, Taylor CM, Loirat C. Pediatr Nephrol. 2007 Jan;22(1):10-6.

A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders. Besbas N, Karpman D, Landau D, Loirat C, Proesmans W, Remuzzi G, Rizzoni G, Taylor CM, Van de Kar N, Zimmerhackl LB; European Paediatric Research Group for HUS. Kidney Int. 2006 Aug;70(3):423-31.

Terminal complement complex (C5b-9) in children with recurrent hemolytic uremic syndrome. Prüfer F, Scheiring J, Sautter S, Jensen DB, Treichl R, Würzner R, Zimmerhackl LB. Semin Thromb Hemost. 2006 Mar;32(2):121-7.

Epidemiology, clinical presentation, and pathophysiology of atypical and recurrent hemolytic uremic syndrome. Zimmerhackl LB, Besbas N, Jungraithmayr T, van de Kar N, Karch H, Karpman D, Landau D, Loirat C, Proesmans W, Prüfer F, Rizzoni G, Taylor MC; European Study Group for Haemolytic Uraemic Syndromes and Related Disorders. Semin Thromb Hemost. 2006 Mar;32(2):113-20.

FH antibodies

Complement factor H-related protein 1 deficiency and factor H antibodies in pediatric patients with atypical hemolytic uremic syndrome. Hofer J, Janecke AR, Zimmerhackl LB, Riedl M, Rosales A, Giner T, Cortina G, Haindl CJ, Petzelberger B, Pawlik M, Jeller V, Vester U, Gadner B, van Husen M, Moritz ML, Würzner R, Jungraithmayr T; German-Austrian HUS Study Group. Clin J Am Soc Nephrol. 2013 Mar;8(3):407-15

Anti-factor H autoantibody-associated hemolytic uremic syndrome: review of literature of the autoimmune form of HUS. Dragon-Durey MA, Blanc C, Garnier A, Hofer J, Sethi SK, Zimmerhackl LB.Semin Thromb Hemost. 2010 Sep;36(6):633-40.

The autoimmune disease DEAP-hemolytic uremic syndrome. Skerka C, Zipfel PF, Müller D, Micklisch S, Riedl M, Zimmerhackl LB, Hofer J. Semin Thromb Hemost. 2010 Sep;36(6):625-32. Epub 2010 Sep 23.