Atipik Hemolitik Üremik Sendrom

Abstract

Hemolitik üremik sendrom HÜS mikroanjiopatik hemolitik anemi, trombositopeni ve akut böbrek hasarının bir arada görüldüğü bir hastalıktır. Hastaların %90’ında klinik tablodan diyareye yol açan Shiga toksin üreten Eschericha Coli STEC sorumludur. Geleneksel olarak “tipik HÜS” olarak adlandırı- lan bu hastalarda iyi bir destek tedavi sağlandığında prognoz yüz güldürücüdür. Hastaların geri kalan %10’u diyare ilişkili olmayan “atipik HÜS” aHÜS olarak adlandırılır. Günümüzde aHÜS’ün patogenezinde kompleman sisteminin regülasyon bozuklukları ve kobalamin metabolizma bozuklukları gibi bir- çok nedenin yer aldığı gösterilmiştir. Bu yeni bilgiler ışığında aHÜS tedavisinde de yeni yaklaşımlar geliştirilmiştir. Bu makalede hastalığın tanı ve tedavisinde güncel bilgiler değer- lendirilmiştir

Keywords

• HÜS,aHÜS,hemolitik üremik sendrom,diyare,eculizumab

Atypical Hemolytic Uremic Syndrome

Abstract

Hemolytic uremic syndrome HUS is characterized by conco- mitancy of hemolysis, thrombocytopenia, and acute kidney injury. The majority of the cases 90% are due to diarrhea D+HUS caused by Shiga toxin-producing Escherichia coli STEC . The prognosis is generally well in HUS patients when appropriate supportive treatment is provided The remaining 10% of the patients have not usually diarrhea and this entity is called atypical HUS aHUS . Nowadays many causes in the etiology of aHUS are discovered, the most important of these being dysregulation of the complement system, and disorders of cobalamine metabolism. In the light of these information novel approaches in the treatment of aHUS have been develo- ped. In this report, current information related to the diagnosis and treatment of HUS have been evaluated

Keywords

• HUS,aHUS,hemolytic uremic syndrome,diarrhea,eculizumab

References

1. 1. Gasser C, Gautier E, Steck A, Siebenmann RE, Oechslin R. Hemolytic-uremic syndrome: Bilateral necrosis of the renal cortex in acute acquired hemolytic anemia. Schweiz Med Wochenschr 1955;85:905-9.
2. 2. Remuzzi G. HUS and TTP: variable expression of a single entity. Kidney Int 1987;32:292-308. http://dx.doi.org/10.1038/ki.1987.206
3. 3. Furlan M, Robles R, Galbusera M, et al. von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic uremic syndrome. N Engl J Med 1998; 339:1578- 84. http://dx.doi.org/10.1056/NEJM199811263392202
4. 4. Jhonson S, Mark Taylor C. Hemolytic uremic syndrome in Avner ED, Harmon WE, Niaudet P, Yoshikawa N eds. Pediatric Nephrology. 6th ed. Berlin Heidelberg: Springer-Verlag. 2009: 1155- 80.
5. 5. Besbas N, Karpman D, Landau D et al. A classification of hemolytic uremic syndrome and thrombotic thrombocytopenic purpura and related disorders. Kidney Int 2006;70:423-31. http://dx.doi.org/10.1038/sj.ki.5001581
6. 6. Karmali MA, Petric M, Lim C, Fleming PC, Arbus GS, Lior H. The association between idiopathic hemolytic uremic syndrome and infection by verotoxin-producing Escherichia coli. J Infect Dis 1985;151:775-82. http://dx.doi.org/10.1093/infdis/151.5.775
7. 7. Grasuri S. Management of hemolytic-uremic syndrome in children. Int J Nephrol Renovasc Dis 2014;7:231-9.
8. 8. Lynn RM, O’Brien SJ, Taylor CM et al. Childhood hemolytic uremic syndrome, United Kingdom and Ireland. Emerg Infect Dis 2005;11:590-6. http://dx.doi.org/10.3201/eid1104.040833

9. 9. Tozzi AE, Caprioli A, Minelli F, Gianviti A, De Petris L, Edefonti A. Shiga-toxin producing Escherichia coli infections associated with hemolytic uremic syndrome, Italy 1988-2000. Emerg Infect Dis 2003;9:106-8. http://dx.doi.org/10.3201/eid0901.020266
10. 10. German EHEC-HUS Registry. The German 2011 epidemic of Shiga toxin-producing E.coli-the nephrological view. Nephrol Dial Transplant 2011;26:2723-6. http://dx.doi.org/10.1093/ndt/gfr462
11. 11. Ekinci Z, Candan C, Alpay H, et al. Hemolytic uremic syndrome outbreak in Turkey in 2011. Turk J Pediatr 2013; 55:246-2.
12. 12. Salvadori M, Bertoni E. Update on hemolytic uremic syndrome: Diagnostic and therapeutic recommendations. World J Nephrol 2013;2:56-76. http://dx.doi.org/10.5527/wjn.v2.i3.56
13. 13. Andreoli SP, Zimmerhacki LB. Hemolytic Uremic Syndrome in Geary DF, Schaefer F eds. Comprehensive Pediatric Nephrology. 1st ed. Philadelphia, PA, USA: Mosby Elsevier. 2008:359- 83.
14. 14. Gerber A, Karch H, Alberger F, et al. 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. J Infect Dis 2002;186:493-500. http://dx.doi.org/10.1086/341940
15. 15. Rowe PC, Orrbine E, Lior H, et al. Risk of hemolytic uremic syndrome after sporadic Escherichia coli O157:H7 infection: results of a Canadian collaborative study. Investigators of the Canadian Pediatric Kidney Disease Research Center. J Pediatr 1998;132:777-82. http://dx.doi.org/10.1016/S0022-3476(98)70303-8
16. 16. Bell BP, Griffin PM, Lozano P, Christie DL, Kobayashi JM, Tarr PI. Predictors of hemolytic uremic syndrome in children during a large outbreak of Escherichia coli O157:H7 infections. Pediatrics 1997;100: E12. http://dx.doi.org/10.1542/peds.100.1.e12
17. 17. Wong CS, Jelacic S, Habeeb RL, Watkins SL, Tarr PI. The risk of the hemolytic-uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 infections. N Engl J Med 2000;342:1930-6. http://dx.doi.org/10.1056/NEJM200006293422601
18. 18. Safdar N, Said A, Gangnon RE, Maki DG. Risk of hemolytic uremic syndrome after antibiotic treatment of Escherichia coli O157:H7 enteritis: a meta-analysis. JAMA 2002;288:996-1001. http://dx.doi.org/10.1001/jama.288.8.996
19. 19. Karmali MA, Steele BT, Petric M, Lim C. Sporadic cases of haemolytic-uraemic syndrome associated with faecal cytotoxin and cytotoxin-producing Escherichia coli in stools. Lancet 1983;1:619-20. http://dx.doi.org/10.1016/S0140-6736(83)91795-6
20. 20. Karmali MA. Infection by verocytotoxin-producing Escherichia coli. Clin Microbiol Rev 1989;2:15-38.
21. 21. Noris M, Mescia F, Remuzzi G. STEC-HUS, atypical HUS and TTP are all diseases of complement activation. Nat Rev Nephrol 2012;8:622-33. http://dx.doi.org/10.1038/nrneph.2012.195
22. 23. Thurman JM, Marians R, Emlen W, et al. Alternative pathway of complement in children with diarrhea-associated hemolytic uremic syndrome. Clin J Am Soc Nephrol 2009;4: 1920-4. http://dx.doi.org/10.2215/CJN.02730409
23. 24. Ståhl A L, Sartz L, Karpman D. Complement activation on platelet-leukocyte complexes and microparticles in enterohemorrhagic Escherichia coli-induced hemolytic uremic syndrome. Blood 2011;117:5503-13. http://dx.doi.org/10.1182/blood-2010-09-309161
24. 25. Louise CB, Obrig TG. Shiga toxin-associated hemolytic uremic syndrome: combined cytotoxic effects of shiga toxin and lipopolysaccharide (endotoxin) on human vascular endothelial cells in vitro. Infect Immun 1992;60:1536-43.
25. 26. Siegler RL. Spectrum of extrarenal involvement in postdiarrheal hemolytic-uremic syndrome. J Pediatr 1994;125:511-8. http://dx.doi.org/10.1016/S0022-3476(94)70001-X
26. 27. Sebbag H, Lemelle JL, Moller C, Schmitt M. Colonic stenosis after hemolytic-uremic syndrome. Eur J Pediatr Surg 1999;9:119-20. http://dx.doi.org/10.1055/s-2008-1072226
27. 28. Teel LD, Daly JA, Jerris RC, Maul D, Svanas G, O’Brien AD et al. Rapid detection of Shiga toxin-producing Escherichia coli by optical immunoassay. J Clin Microbiol 2007;45(10): 3377-80. http://dx.doi.org/10.1128/JCM.00837-07
28. 29. Cochran JB, Panzarino VM, Maes LY, Tecklenburg FW. Pneumococcus-induced T-antigen activation in hemolytic uremic syndrome and anemia. Pediatr Nephrol 2004;19:317-21. http://dx.doi.org/10.1007/s00467-003-1382-z
29. 30. Sellier-Leclerc AL, Frémeaux-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;18:2392-400. http://dx.doi.org/10.1681/ASN.2006080811
30. 31. Moake JL, Byrnes CK, Troll JH, et al. Unusually large plasma factorVIII: von Willebrand factor multimers in chronic relapsing thrombotic thrombocytopenic purpura. N Eng J Med 1982;307:1432-5. http://dx.doi.org/10.1056/NEJM198212023072306
31. 32. Furlan M, Robles R, Solenthaler M, et al. Deficient activity of von Willebrand factor-cleaving protease in chronic relapsing thrombotic thrombocytopenic purpura. Blood 1997;89: 3097-103.
32. 33. Fujikawa K, Suziki H, McMullen B, Chung D. Purification of human von Willebrand factor cleaving proteaseand its identification as a new member of the metalloproteinase family. Blood 2001;98:1662-6. http://dx.doi.org/10.1182/blood.V98.6.1662
33. 34. Lammle B, George JN. Thrombotic thrombocytopenic purpura: advances in pathophysiology, diagnosis, and treatment-introduction. Semin Hematol 2004;41(1):1-3. http://dx.doi.org/10.1053/j.seminhematol.2003.11.001
34. 35. Kaplan SB, Ruebner RL, Spinale JM, Copelovitch L. Current treatment of atypical hemolytic uremic syndrome. Intractable Rare Dis Res 2014;3:34-5. http://dx.doi.org/10.5582/irdr.2014.01001
35. 36. Caprioli J, Castelletti F, Bucchioni S, et al. Complement factor H mutations and gene polymorphisms in haemolytic uraemic syndrome: the C-257T, the A2089G and the G2881T polymorphisms are strongly associated with the disease. Hum Mol Genet 2003;15:3385-95. http://dx.doi.org/10.1093/hmg/ddg363
36. 37. de Córdoba SR, de Jorge EG. Translational mini-review series on complement factor H: genetics and disease associations of human complement factor H. Clin Exp Immunol 2008; 151:1-13. http://dx.doi.org/10.1111/j.1365-2249.2007.03552.x
37. 38. Lee BH, Kwak SH, Shin JI et al. Atypical hemolytic uremic syndrome associated with complement factor H autoantibodies and CFHR1/CFHR3 deficiency. Pediatr Res 2009;66:336-40. http://dx.doi.org/10.1203/PDR.0b013e3181b1bd4a
38. 39. Verhave JC, Wetzels JFM, van de Kar NCAJ. Novel aspects of atypical haemolytic uraemic syndrome and the role of eculizumab. Nephrol Dial Transplant 2014;29:131-41. http://dx.doi.org/10.1093/ndt/gfu235
39. 40. Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis 2011;6:60. http://dx.doi.org/10.1186/1750-1172-6-60
40. 41. Geraghty MT, Perlman EJ, Martin LS, et al. Cobalamin C defect associated with hemolyticuremic syndrome. J Pediatr 1992;120:934-7. http://dx.doi.org/10.1016/S0022-3476(05)81967-5
41. 42. Menni F, Testa S, Guez S, Chiarelli G, Alberti L, Esposito S.s Neonatal atypical hemolytic uremic syndrome due to methylmalonic aciduria and homocystinuria. Pediatr Nephrol 2012;27:1401-5. http://dx.doi.org/10.1007/s00467-012-2152-6
42. 43. Cornec-Le Gall E, Delmas Y, De Parscau L, et al. Adult-onset eculizumab-resistant hemolytic uremic syndrome associated with cobalamin C deficiency. Am J Kidney Dis 2014; 63:119-23. http://dx.doi.org/10.1053/j.ajkd.2013.08.031
43. 44. Lemaire M, Frémeaux-Bacchi V, et al. Recessive mutations in DGKE cause atypical hemolyticuremic syndrome. Nat Genet 2013;45:531-6. http://dx.doi.org/10.1038/ng.2590
44. 45. Ariceta G, Besbas N, Johnson S. Guideline for the investigation and initial therapy of diarrheanegative hemolytic uremic syndrome. Pediatr Nephrol 2009;24:687-96. http://dx.doi.org/10.1007/s00467-008-0964-1
45. 46. Vaisbich MH. Hemolytic-Uremic Syndrome in childhood. J Bras Nefrol 2014;36:208-20. http://dx.doi.org/10.5935/0101-2800.20140032
46. 47. Sinha A, Gulati A, Saini S, et al. Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody- associated hemolytic uremic syndrome in children. Kidney Int 2014;85:1151-60. http://dx.doi.org/10.1038/ki.2013.373
47. 48. Hillmen P, Hall C, Marsh JC, Elebute M, Bombara MP, Petro BE, et al. Effect of eculizumab on hemolysis and transfusion requirements in patients with paroxysmal nocturnal hemoglobinuria. N Engl J Med 2004;350:552-9.
48. 49. Legendre CM, Licht C, Loirat C. Eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 2013;369:1379-80.
49. 50. Legendre CM, Licht C, Muus P, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med 2013;368:2169-81.
50. 51. Gruppo RA, Rother RP. Eculizumab for congenital atypical hemolytic-uremic syndrome. N Engl J Med 2009;360:544-6.
51. 52. Ariceta G, Arrizabalaga B, Aguirre M, Morteruel E, Lopez-Trascasa M. Eculizumab in the treatment of atypical hemolytic uremic syndrome in infants. Am J Kidney Dis 2012;59:707-10.
52. 53. Bouts A, Monnens L, Davin JC, Struijk G, Spanjaard L. Insufficient protection by Neisseria meningitidis vaccination alone during eculizumab therapy. Pediatr Nephrol 2011;26: 1919-20.
53. 54. Loirat C, Niaudet P. The risk of recurrence of hemolytic uremic syndrome after renal transplantation in children. Pediatr Nephrol 2003:18:1095-101.
54. 55. Ferraris JR, Ramirez JA, Ruiz S, et al. Shiga toxin-associated hemolytic uremic syndrome: Absence of recurrence after renal transplantation. Pediatr Nephrol 2002:17:809-14.
55. 56. Frémeaux-Bacchi V, Arzouk N, Ferlicot S, Charpentier B, Snanoudj R, Dürrbach A. Recurrence of HUS due to CD46/ MCP mutation after renal transplantation: a role for endothelial microchimerism. Am J Transplant 2007;7:2047-51.
56. 57. Seitz B, Albano L, Vocila F et al. Recurrence of hemolytic uremic syndrome after renal transplantation. Transplant Proc 2007;39:2583-5.
57. 58. Dragon-Durey MA, Sethi SK, Bagga A et al. Clinical features of anti-factor H autoantibody associated hemolytic uremic syndrome. J Am Soc Nephrol 2010;21:2180-7.
58. 59. Loirat C, Fremeaux-Bacchi V. Hemolytic uremic syndrome recurrence after renal transplantation. Pediatr Transplant 2008;12:619-29.