Atypical Hemolytic Uremic Syndrome, literature revision and consensus document. Diagnosis and treatment
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Atypical Hemolytic Uremic Syndrome
Thrombotic microangiopathy
Renal transplant

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Córdoba JP, Contreras KM, Larrarte C, Espitaleta Z, González LE, Ibarra M, Echeverri JE, Carrascal M, Valderrama LA, Prada M. Atypical Hemolytic Uremic Syndrome, literature revision and consensus document. Diagnosis and treatment. Rev. Colomb. Nefrol. [Internet]. 2015 Mar. 6 [cited 2022 Jan. 21];2(1):19-40. Available from:


Atypical Hemolytic Uremic Syndrome is an ultra-orphan disease, more than 50% of patients die, need renal replacement therapy or have permanent renal failure within the first year of diagnostic. With current supportive care 9-15% of aHUS patients die within 1 year following a clinical manifestation of aHUS. Severe consequences of this disease reinforce the early diagnostic and treatment importance. Clinical manifestations of this disease include the classic triad of microangiopatic anemia, thrombocytopenia and end organ damage where the renal failure is the most common manifestation, although not the only one as neurological, cardiac and gastrointestinal complications are also apparent. Mutations on the complement system regulating proteins are recognized as the cause of this syndrome; however they are not identified in all patients as new mutations are continuously being identified. It has a high rate post-transplantation graft loss in 60% of the cases. Most known therapy for this disease, considered as the first line therapy was plasmapheresis; however it shows very poor results. Since 2011 we have a recombinant monoclonal antibody targeted to the complement component C5 (eculizumab), the only approved for the treatment of aHUS, which has proven to significantly improve the disease prognosis and progression, and is considered the first line therapy.
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1. Josep M. Campistol et al.: Actualización en síndrome hemolítico urémico atípico: diagnóstico y tratamiento. Documento de consenso; Nefrología 2013;33(1):27-45.

2. Noris, M., Caprioli, J., Bresina, E., Mossali, C., Pianetti, G., et al. Relative Role of genetic Complement abnormalities in Sporadic and Familial aHUS and Their Impact on Clinical Phenotype. Clin J Am Soc Nephrol 5(10):1844 -1859, 2010.

3. Noris, M., Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med, 2009;361(17):1676–1687.

4. Noris M,. Bucchioni S,. Galbusera M et al. Complement factor H mutation in familial thrombotic thrombocytopenic purpuraeith ADAMTS13 deficiency and renal involvement. J Am Soc Nephrol, 2005;16(5):1177-1183.

5. Taylor CM, Machin S, Wigmore SJ, Goodship TH. Clinical practice guidelines for the management of atypical haemolytic uraemic syndrome in the United Kingdom. Br J Haematol, 2010;148(1):37-47.

6. Keating G. Eculizumab: A Riview of its use in atypical haemolytic uremic syndrome. Drugs, 2013;73(18):2053-2066.

7. Caprioli, J., Noris, M., Brioschi, S., Pianetti, G., Castelletti, F., et al. Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment and outcome. Blood 2006;108:1267-1279.

8. Constantinescu AR, Bitzan M, Weiss LS, et al. Non-enteropathic hemolytic uremic syndrome: causes and short-term course. Am J Kidney Dis, 2004;43(6):976-982.

9. Vesely SK, George JN, Lammle B, et al. ADAMTS13 activity in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: relation to presenting features and clinical outcomes in a prospective cohort of 142 patients. Blod, 2003;102(1):60-68.

10. Neuhaus TJ, Calonder S, Leumann EP. Heterogeneity of atypical haemolytic uraemic syndromes. Arch Dis Child, 1997;76(6):518- 21.

11. George JN, Kremer Hovinga JA, Terrell DR, Vesely SK, Lammle B. The Oklahoma Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome Registry: The Swiss connection. Eur J Haematol, 2008;80(4):277-286.

12. Langman C. Systemic multi-organ complications in atypical haemolytic uremic syndrome (aHUS): Retrospective study in a medical practice setting. European Hematology Association, Abstract 409, 2012;June 14-17.

13. Sellier-Leclerc AL, Fremeaux-Bacchi V, Dragon-Durey MA, et al. Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol, 2007;18(8):2392-2400.

14. Bu F, Borsa N, Gianluigi A, et al. Familial atypical Hemolytic Uremic Syndrome: a Review of its genetic and clinical aspects. Clinical and Developmental Immunology, 2012; Pag 1-9.

15. Schmidtko J, Peine S, El-Housseini Y, Pascual M, and Meier P, et al. Treatment of Atypical Hemolytic Uremic Syndrome
and Thrombotic Microangiopathies: A focus on Eculizumab. Am J Kidney Dis, 2013;61(2):289-299.

16. Meri S. Complement activation in diseases presenting with thrombotic microangiopathy.Eur J Intern Med, 2013;24

17. Heinen S, Pluthero FG, van Eimeren VF, Quaggin SE, Licht C. Monitoring and modeling treatment of atypical hemolytic uremic syndrome. Molecular Immunology, 2013;54(1):84-88.

18. Cofiell R, Kukreja A, Bedard K, et al. Biomarkers of complement activation, inflammation, endothelial activation and damage, thrombosis and renal injury in patients with atypical hemolytic uremic syndrome (aHUS) prior to and during treatment with eculizumab. American society of Hematology, Abstract/poster Presentation Number 2184, 2013.

19. Loriat C, Fremeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet Journal of rare Diseases, 2011;6(1):60.

20. Ve´ronique Fremeaux-Bacchi et al.: Genetics and Outcome of Atypical Hemolytic Uremic Syndrome: A Nationwide French Series Comparing Children and Adults; Clin J Am Soc Nephrol, Vol 8 April, 2013.

21. Guo X, Nzerue C. How to prevent, recognize, and treat drug/induced nephrotoxicity. Cleve Clin J Med, 2002;69(4):289-4, 296.

22. Blake-Haskins JA, Lechleider RJ, Kreitman RJ. Thrombotic microangiopathy with targeted cancer agents. Clin Cancer Res, 2011;17(18):5858-5866.

23. Marik PE, Rivera R. Hypertensive emergencies: an update. Curr Opin Crit Care, 2011;17(6):569-580.

24. Van den born BJ, Honnebier UP, koopmans RP, van Montfrans GA. Microangiopathic hemolysis and renal failure in malignant hypertension. Hypertension, 2005;45(2):246-251.

25. Devinsky O, Petito CK, Alonso DR. Clinical and neuropathological findings in systemic lupus erythematosus: the role of vasculitis, herat emboli, and thrombotic thrombocytopenic purpura. Ann Neurol, 1998;23(4):380-384.

26. Mok C, Raymond C, Kwok L, et al. Effect of renal disease on the standardized mortality ratio and life expectancy of patients with systemic lupus erythematousus. Arthritis and Rheumatism, 2013;65 (8):2154-2160.

27. Richani K, soto E, Romero R, et al. Normal pregnancy is characterized by systemic activation of complement system. J Matern Fetal Neonatal Med, 2005;17(4):239-245.

28. Goodship THJ, Kavanagh D. Pulling the trigger in atypical hemolytic uremic syndrome: the role of pregnancy. Journal
of the American Society of nephrology, 2010;21(5):731-732.

29. Kakhouri F, Roumenina L, Provot F, et al. Pregnancy-associated hemolytic uremic syndrome revisited in the era of complement gene mutations. J Am soc Nephrol, 2010;21(5):859-867.

30. Salmon JE, Heuser C, Triebwasser M, et al. Mutations in complement regulatory proteins predispose to preeclampsia:
a genetic analysis of the PROMISSE cohort. PLoS Med, 2011;8(3):e1001013.

31. Coppo P, Schwarzinger M, Buffet M, et al. Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA Reference Center Experience. PLoS ONE, 2010;5(4): e10208.

32. Ferrari S, Scheiflinger F, Rieger M, et al. Prognostic value of anti-ADAMTS 13 antibody features (Ig isotype, titer, and inhibitory effect) in a cohort of 35 adult French patients undergoing a first episode of thrombotic microangiopathy with undetectable ADAMTS 13 activity. Blood, 2007;109(7):2815-2822.

33. Cataland SR, Yang S, Wu HM. The use of ADAMTS13 activity, platelet count, and serum creatinine to differentiate acquired thrombotic thrombocytopenic purpura from other thrombotic microangiopathies. British Journal of Haematology, 2012;157(4):501-503.

34. Bentley MJ, Lehman CM, Blaylock RC, Wilson AR, Rodgers GM. The utility of patient characteristics in predicting severe ADAMTS13 deficiency and response to plasma exchange. Transfusion, 2010;50(8):1654-1664.

35. Rodríguez de Córdoba, S., Montes, T. Síndrome hemolítico urémico atípico. Nefrologia Sup Ext 2011;2(81):58-65.

36. Westra, D., Wetzwlwa, JFM., Volokhina, EB., van den Heuvel, LP., van de Kar., NCAJ. A new era in the diagnosis and treatment of atypical haemolytic uraemic syndrome. Netherlands The Journal of Medicine 3: Vol 70, pag 121-129, 2012.

37. Richards A, Kemp EJ, Liszewski MK, Goodship JA, Lampe AK, Decorte R, Müslümano?lu MH, Kavukcu S, Filler G, Pirson Y, Wen LS, Atkinson JP, Goodship TH. Mutations in human complement regulator, membrane cofactor protein (CD46), predispose to development of familial hemolytic uremic syndrome.Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):12966-71. Epub 2003 Oct 17.

38. Bu, F., Borsa, N., Gianluigi, A., Smith, RJH. Familial Atypical Hemolytic Uremic Syndrome: A review of Its Genetic and Clinical Aspects. Clinical and developmental Immunology. Vol 2012, Article ID 370426, 9 pages.

39. Caprioli J, Bettinaglio P, Zipfel PF, Amadei B, Daina E, Gamba S, et al. The molecular basis of familial hemolytic uremic syndrome: mutation analysis of factor H gene reveals a hot spot in short consensus repeat 20. J Am Soc Nephrol 2001;12(2):297-307.

40. Fremeaux-Bacchi, V., Fakhouri, F., Garnier, A., Bienaimé, F., Dragón-Durey, M., Ngo, S., et al. Genetics and Outcome of Atypical Hemolytic Uremic Syndrome: A Nationwide French Series Comparing Children and Adults. Clin J Am Soc Nephrol 8: xxx-xxx(Falta información?), 2013. Doi: 10.2215/CJN.04760512.

41. Delvaeye, M., Noris, M., De Vriese, A., Esmon, CT., Esmon, NL. Thrombomodulin mutations in Atypical Hemolytic- Uremic Syndrome. N Engl J Med 2009;361:345-357.

42. De Jorge, E. G. et al. The development of atypical hemolytic uremic syndrome depends on complement C5. J. Am.
Soc. Nephrol 2011;22:137–145.

43. Pickering, M. C. et al. Spontaneous hemolytic uremic syndrome triggered by complement factor H lacking surface recognition domains.J. Exp. Med. 2007;204:1249–1256.

44. Clark WF. Thrombotic microangiopathy: Current knowledge and outcomes with plasma exchange. Seminars in dialysis, 2012;25(2):214-219.

45. Heinen S, Pluthero FG, van Eimeren VF, Quaggin SE, Licht C. Monitoring and modeling treatment of atypical hemolytic uremic syndrome. Molecular Immunology, 2013;54(1):84-88.

46. Riedl M, Hofe J, rosales A, Wurzner R, and Jungraithmayr T. Acute manifestation and 1 year follow up of a big cohort of patients with atypical hemolytic uremic syndrome (aHUS). J am Soc Nephrol, 2011; 22.(faltan las páginas)

47. Taylor CM, Chua C, Howie AJ, Risdon RA.Clinico-pathological findings in diarrhea-negative haemolytic uraemic syndrome. Pediatric Nephrology, 2004;19(4):419-425.

48. Delmas Y, Loirat C, Muus P, et al. Eculizumab (ECU) in atypical hemolytic uremic syndrome (aHUS) patients with long disease duration and chronic kidney disease (CKD): sustained efficacy at 3 years. American Society of Nephrology, Kidney week, 2013.

49. Greenbaum L, Babu S, Furman R, et al. Continued improvements in renal function with sustained Eculizumab (ECU) in patients with atypical hemolytic uremic syndrome (aHUS) resistant to plasma exchange/infusion (PE/PI). J Am Soc Nephrol, 2011a; 22. (faltan las páginas)

50. Licht C, Muus P, Legendre C, et al. Ph II study of Eculizumab in patients with atypical hemolytic uremic syndrome (aHUS) receiving chronic plasma exchange/infusion (PE/PI). American Society of Nephrology, Abstract TH-PO366, 2011a.

51. Muus P, Legendre C, Douglas K, et al. Safety and efficacy of Eculizumab in aHUS patients on chronic plasma therapy: Interim analysis from a phase II trial. American Society of Nephrology meeting, Renal Week 2010, Denver, CO. J Am Soc Nephrol, 2010.

52. Gaber O, Loirat C, Greenbaum L, et al. Eculizumab maintains efficacy in atypical hemolytic uremic syndrome (aHUS) patients with progressing thrombotic microangiopathy (TAM): 3 year update. American Society of Nephrolo gy Kidney Week, 2013.

53. Vilalta R, Al-Akash S, Davin JC, et al. Eculizumab therapy for pediatric patients with atypical haemolytic uremic syndrome: Efficacy and safety outcomes of a retrospective study. European Hematology Association, Abstract 115, 2012.

54. Legendre C, Licht C, Muus P, et al. Terminal Complement inhibitor Eculizumab in atypical Hemolytic Uremic syndrome. N Engl J Med, 2013;368:2169-81.

55. Fakhouri F, Hourmant M, Campistol J, et al. Eculizumab inhibits thrombotic microangiopathy and improves renal function in adult atypical hemolytic uremic syndrome patients. American Society of Nephrology, Kidney Week, 2013.

56. Electronic Medicines Compendium.Soliris—Summary of Product Characteristics [online], uk/emc/medicine/19966/SPC/soliris/ (2012).

57. U. S. Food and Drug Administration. Highlights of Prescribing Information: Soliris [online], http://www.accessdata. (2011).
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