The hemolytic uremic syndrome: a possible etiological role of Campylobacter infection

Cover Page


Cite item

Full Text

Abstract

Hemolytic uremic syndrome (HUS), one of the forms of thrombotic microangiopathy, is a severe emergency with non-immune (Coombs negative) anemia, thrombocytopenia and acute renal injury. HUS is heterogeneous, and its most common form, the typical HUS, is associated with Shiga toxin (Stx) producing bacteria, such as Escherichia coli, Shigella dysenteriae, and Citrobacter freundii. Less frequent is HUS, caused by a neuraminidase producing streptococcus (pneumococcal HUS). The most uncommon form is the atypical HUS, which is a genetic orphan disease associated with an abnormality in the regulatory protein of the complement system. HUS has a fairly high mortality rate, amounting to 10–15% on average. The long-term outcomes of HUS depend on its type, as well as on the degree of the primary body tissue damage. According to the data from Novosibirsk Children's Municipal Clinical Hospital No 3 from 1991, 44 cases of HUS in children have been identified. Complete recovery, without any residual abnormalities, was registered in 25 children (56.8% of the cases). Nine children (20.5%) developed chronic kidney disease and 10 (22.7%) of all HUS cases were fatal. Early diagnosis, as well as the identification of pathogenetic mechanisms, is the basis for adequate therapy and outcome prediction. Campylobacter may be one of the causative agents of HUS. Despite new cases of Campylobacter-associated HUS being registered in the world, the very possibility of HUS induction by this pathogen and its pathophysiology are currently unclear. There is no convincing evidence for both Stx and the neuraminidase-related mechanism of HUS in Campylobacter infections. Given the high incidence of autoimmune disorders like Guillain-Barre syndrome and reactive arthritis in Campylobacter infections, it is currently impossible to exclude an autoimmune mechanism of HUS in these diseases. Thus, the role of Campylobacter, as a new potential bacterial agent of HUS, as well as the pathogenesis of such conditions in Campylobacter infections, requires further study.

About the authors

G. S. Karpovich

Novosibirsk State Medical University

Author for correspondence.
Email: karpovich.gleb@yandex.ru
ORCID iD: 0000-0003-0982-6952

Gleb S. Karpovich – MD, Assistant, Chair of Infectious Diseases

62 Dem'yana Bednogo ul., Novosibirsk, 630005

 Tel.: +7 (913) 725 11 69

Россия

E. I. Krasnova

Novosibirsk State Medical University

Email: krasnova-inf@rambler.ru
ORCID iD: 0000-0003-3168-9309

Elena I. Krasnova – MD, PhD, Professor, Head of the Chair of Infectious Diseases

52 Krasnyy prospekt, Novosibirsk, 630091

Россия

A. V. Vasyunin

Novosibirsk State Medical University

Email: aleksandr.vasyunin1949@yandex.ru
ORCID iD: 0000-0003-4288-5348

Aleksandr V. Vasyunin – MD, PhD, Professor, Chair of Infectious Diseases

52 Krasnyy prospekt, Novosibirsk, 630091

Россия

T. V. Komissarova

Novosibirsk Children's Municipal Clinical Hospital No. 3

Email: dgkb3@nso.ru

Tatiana V. Komissarova – MD, PhD, Head Physician

81 Okhotskaya ul., Novosibirsk, 630040

Россия

L. I. Enivatova

Novosibirsk Children's Municipal Clinical Hospital No. 3

Email: dgkb3@nso.ru

Liliya I. Enivatova – MD, Resuscitator, Head of Intensive Care Unit

81 Okhotskaya ul., Novosibirsk, 630040

Россия

O. V. Gaynts

Novosibirsk Children's Municipal Clinical Hospital No. 3

Email: dgkb3@nso.ru

Oleg V. Gaynts – MD, Resuscitator, Intensive Care Unit

81 Okhotskaya ul., Novosibirsk, 630040

Россия

References

  1. Fakhouri F, Vercel C, Frémeaux-Bacchi V. Obstetric nephrology: AKI and thrombotic microangiopathies in pregnancy. Clin J Am Soc Nephrol. 2012;7(12):2100–6. doi: 10.2215/CJN.13121211.
  2. Fakhouri F. Pregnancy-related thrombotic microangiopathies: Clues from complement biology. Transfus Apher Sci. 2016;54(2):199–202. doi: 10.1016/j.transci.2016.04.009.
  3. Garg AX, Suri RS, Barrowman N, Rehman F, Matsell D, Rosas-Arellano MP, Salvadori M, Haynes RB, Clark WF. Long-term renal prognosis of diarrhea-associated hemolytic uremic syndrome: a systematic review, meta-analysis, and meta-regression. JAMA. 2003;290(10):1360–70. doi: 10.1001/jama.290.10.1360.
  4. Mead PS, Griffin PM. Escherichia coli O157:H7. Lancet. 1998;352(9135):1207–12. doi: 10.1016/S0140-6736(98)01267-7.
  5. Milford D. The hemolytic uremic syndromes in the United Kingdom. In: Hemolytic Uremic Syndrome and Thrombotic Thrombocytopenic Purpura. New York: Marcel Dekker; 1992. p. 39–59.
  6. E. coli. World health organization [Internet]. Available from: https://www.who.int/news-room/fact-sheets/detail/e-coli.
  7. Ruggenenti P, Noris M, Remuzzi G. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int. 2001;60(3):831–46. doi: 10.1046/j.1523-1755.2001.060003831.x.
  8. Сenter for disease control and prevention. Hemolytic Uremic Syndrome, Post-diarrheal [Internet]. Available from: https://wwwn.cdc.gov/nndss/conditions/hemolytic-uremic-syndrome-post-diarrheal/.
  9. Michael M, Elliott EJ, Craig JC, Ridley G, Hodson EM. Interventions for hemolytic uremic syndrome and thrombotic thrombocytopenic purpura: a systematic review of randomized controlled trials. Am J Kidney Dis. 2009;53(2):259–72. doi: 10.1053/j.ajkd.2008.07.038.
  10. Cobeñas CJ, Alconcher LF, Spizzirri AP, Rahman RC. Long-term follow-up of Argentinean patients with hemolytic uremic syndrome who had not undergone dialysis. Pediatr Nephrol. 2007;22(9):1343–7. doi: 10.1007/s00467-007-0522-2.
  11. World Health Organization. Outbreak of haemolytic uraemic syndrome in Germany [Internet]. Available from: https://www.who.int/csr/don/2011_05_27/en/.
  12. Brooks JT, Bergmire-Sweat D, Kennedy M, Hendricks K, Garcia M, Marengo L, Wells J, Ying M, Bibb W, Griffin PM, Hoekstra RM, Friedman CR. Outbreak of Shiga toxin-producing Escherichia coli O111:H8 infections among attendees of a high school cheerleading camp. Clin Infect Dis. 2004;38(2):190–8. doi: 10.1086/380634.
  13. Caprioli A, Luzzi I, Rosmini F, Pasquini P, Cirrincione R, Gianviti A, Matteucci MC, Rizzoni G. Hemolytic-uremic syndrome and Vero cytotoxin-producing Escherichia coli infection in Italy. The HUS Italian Study Group. J Infect Dis. 1992;166(1):154–8. doi: 10.1093/infdis/166.1.154.
  14. Lopez EL, Diaz M, Grinstein S, Devoto S, Mendilaharzu F, Murray BE, Ashkenazi S, Rubeglio E, Woloj M, Vasquez M, et al. Hemolytic uremic syndrome and diarrhea in Argentine children: the role of Shiga-like toxins. J Infect Dis. 1989;160(3):469–75. doi: 10.1093/infdis/160.3.469.
  15. McCarthy TA, Barrett NL, Hadler JL, Salsbury B, Howard RT, Dingman DW, Brinkman CD, Bibb WF, Cartter ML. Hemolytic-Uremic Syndrome and Escherichia coli O121 at a Lake in Connecticut, 1999. Pediatrics. 2001;108(4):E59. doi: 10.1542/peds.108.4.e59.
  16. Sonntag AK, Prager R, Bielaszewska M, Zhang W, Fruth A, Tschäpe H, Karch H. Phenotypic and genotypic analyses of enterohemorrhagic Escherichia coli O145 strains from patients in Germany. J Clin Microbiol. 2004;42(3):954–62. doi: 10.1128/jcm.42.3.954-962.2004.
  17. Thorpe CM. Shiga toxin-producing Escherichia coli infection. Clin Infect Dis. 2004;38(9):1298–303. doi: 10.1086/383473.
  18. Srivastava RN, Moudgil A, Bagga A, Vasudev AS. Hemolytic uremic syndrome in children in northern India. Pediatr Nephrol. 1991;5(3):284–8. doi: 10.1007/bf00867477.
  19. Guerin PJ, Brasher C, Baron E, Mic D, Grimont F, Ryan M, Aavitsland P, Legros D. Shigella dysenteriae serotype 1 in west Africa: intervention strategy for an outbreak in Sierra Leone. Lancet. 2003;362(9385):705–6. doi: 10.1016/S0140-6736(03)14227-4.
  20. Houdouin V, Doit C, Mariani P, Brahimi N, Loirat C, Bourrillon A, Bingen E. A pediatric cluster of Shigella dysenteriae serotype 1 diarrhea with hemolytic uremic syndrome in 2 families from France. Clin Infect Dis. 2004;38(9):e96–9. doi: 10.1086/383474.
  21. Tschape H, Prager R, Streckel W, Fruth A, Tietze E, Böhme G. Verotoxinogenic Citrobacter freundii associated with severe gastroenteritis and cases of haemolytic uraemic syndrome in a nursery school: green butter as the infection source. Epidemiol Infect. 1995;114(3):441–50. doi: 10.1017/s0950268800052158.
  22. Trachtman H, Austin C, Lewinski M, Stahl RA. Renal and neurological involvement in typical Shiga toxin-associated HUS. Nat Rev Nephrol. 2012;8(11):658–69. doi: 10.1038/nrneph.2012.196.
  23. Fraser ME, Fujinaga M, Cherney MM, Melton-Celsa AR, Twiddy EM, O'Brien AD, James MN. Structure of shiga toxin type 2 (Stx2) from Escherichia coli O157:H7. J Biol Chem. 2004;279(26):27511–7. doi: 10.1074/jbc.M401939200.
  24. Tesh VL, Burris JA, Owens JW, Gordon VM, Wadolkowski EA, O'Brien AD, Samuel JE. Comparison of the relative toxicities of Shiga-like toxins type I and type II for mice. Infect Immun. 1993;61(8):3392–402.
  25. Louise CB, Obrig TG. Specific interaction of Escherichia coli O157:H7-derived Shiga-like toxin II with human renal endothelial cells. J Infect Dis. 1995;172(5):1397–401. doi: 10.1093/infdis/172.5.1397.
  26. Jenkins C, Willshaw GA, Evans J, Cheasty T, Chart H, Shaw DJ, Dougan G, Frankel G, Smith HR. Subtyping of virulence genes in verocytotoxin-producing Escherichia coli (VTEC) other than serogroup O157 associated with disease in the United Kingdom. J Med Microbiol. 2003;52(Pt 11):941–7. doi: 10.1099/jmm.0.05160-0.
  27. Siegler RL, Obrig TG, Pysher TJ, Tesh VL, Denkers ND, Taylor FB. Response to Shiga toxin 1 and 2 in a baboon model of hemolytic uremic syndrome. Pediatr Nephrol. 2003;18(2):92–6. doi: 10.1007/s00467-002-1035-7.
  28. Acheson DW, Moore R, De Breucker S, Lincicome L, Jacewicz M, Skutelsky E, Keusch GT. Translocation of Shiga toxin across polarized intestinal cells in tissue culture. Infect Immun. 1996;64(8):3294–300.
  29. Bitzan M, Richardson S, Huang C, Boyd B, Petric M, Karmali MA. Evidence that verotoxins (Shiga-like toxins) from Escherichia coli bind to P blood group antigens of human erythrocytes in vitro. Infect Immun. 1994;62(8):3337–47.
  30. Cooling LL, Walker KE, Gille T, Koerner TA. Shiga toxin binds human platelets via globotriaosylceramide (Pk antigen) and a novel platelet glycosphingolipid. Infect Immun. 1998;66(9):4355–66.
  31. van Setten PA, Monnens LA, Verstraten RG, van den Heuvel LP, van Hinsbergh VW. Effects of verocytotoxin-1 on nonadherent human monocytes: binding characteristics, protein synthesis, and induction of cytokine release. Blood. 1996;88(1):174–83.
  32. te Loo DM, Monnens LA, van Der Velden TJ, Vermeer MA, Preyers F, Demacker PN, van Den Heuvel LP, van Hinsbergh VW. Binding and transfer of verocytotoxin by polymorphonuclear leukocytes in hemolytic uremic syndrome. Blood. 2000;95(11):3396–402.
  33. Ohmi K, Kiyokawa N, Takeda T, Fujimoto J. Human microvascular endothelial cells are strongly sensitive to Shiga toxins. Biochem Biophys Res Commun. 1998;251(1):137–41. doi: 10.1006/bbrc.1998.9417.
  34. Министерство здравоохранения Российской Федерации. Союз педиатров России. Федеральные клинические рекомендации по оказанию медицинской помощи детям с гемолитико-уремическим синдромом. М.; 2015. 27 с. [Интернет]. Доступно на: https://www.vodkb.ru/wp-content/uploads/2017/03/gus.pdf.
  35. Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med. 2009;361(17):1676–87. doi: 10.1056/NEJMra0902814.
  36. Nathanson S, Deschênes G. Prognosis of Streptococcus pneumoniae-induced hemolytic uremic syndrome. Pediatr Nephrol. 2001;16(4):362–5. doi: 10.1007/s004670100564.
  37. Constantinescu AR, Bitzan M, Weiss LS, Christen E, Kaplan BS, Cnaan A, Trachtman H. Non-enteropathic hemolytic uremic syndrome: causes and short-term course. Am J Kidney Dis. 2004;43(6):976–82. doi: 10.1053/j.ajkd.2004.02.010.
  38. Научное общество нефрологов России. Клинические рекомендации по диагностике и лечению атипичного гемолитико-уремического синдрома. Нефрология и диализ. 2015;17(3):242–64.
  39. Cochran JB, Panzarino VM, Maes LY, Tecklenburg FW. Pneumococcus-induced T-antigen activation in hemolytic uremic syndrome and anemia. Pediatr Nephrol. 2004;19(3):317–21. doi: 10.1007/s00467-003-1382-z.
  40. Huang DT, Chi H, Lee HC, Chiu NC, Huang FY. T-antigen activation for prediction of pneumococcus-induced hemolytic uremic syndrome and hemolytic anemia. Pediatr Infect Dis J. 2006;25(7):608–10. doi: 10.1097/01.inf.0000223494.83542.ad.
  41. von Vigier RO, Seibel K, Bianchetti MG. Positive Coombs test in pneumococcus-associated hemolytic uremic syndrome. A review of the literature. Nephron. 1999;82(2):183–4. doi: 10.1159/000045396.
  42. von Vigier RO, Fossali E, Crosazzo L, Bianchetti MG. Positive Coombs test in postpneumococcal hemolytic-uremic syndrome. Pediatr Infect Dis J. 2005;24(11):1028–9. doi: 10.1097/01.inf.0000187032.38556.b3.
  43. Pan CG, Leichter HE, Werlin SL. Hepatocellular injury in Streptococcus pneumoniae-associated hemolytic uremic syndrome in children. Pediatr Nephrol. 1995;9(6):690–3. doi: 10.1007/bf00868713.
  44. Шпикалова ИЮ, Панкратенко ТЕ, Эмирова ХМ, Зверев ДВ, Толстова ЕМ. Поражение ЦНС у больных с Шига-токсин ассоциированным гемолитико-уремическим синдромом (STEC-ГУС): современные аспекты патогенеза, клиники и стратегии лечения (Обзор литературы). Нефрология и диализ. 2014;16(3):328–38.
  45. Oakes RS, Kirkham JK, Nelson RD, Siegler RL. Duration of oliguria and anuria as predictors of chronic renal-related sequelae in post-diarrheal hemolytic uremic syndrome. Pediatr Nephrol. 2008;23(8):1303–8. doi: 10.1007/s00467-008-0799-9.
  46. Copelovitch L, Kaplan BS. Streptococcus pneumonia – Associated Hemolytic Uremic Syndrome: Classification and the Emergence of Serotype 19A. Pediatrics. 2010;125(1):e174–82. doi: 10.1542/peds.2007-2017.
  47. Proulx F, Sockett P. Prospective surveillance of Canadian children with the haemolytic uraemic syndrome. Pediatr Nephrol. 2005;20(6):786–90. doi: 10.1007/s00467-005-1843-7.
  48. Vanderkooi OG, Kellner JD, Wade AW, Jadavji T, Midgley JP, Louie T, Tyrell GJ. Invasive Streptococcus pneumoniae infection causing hemolytic uremic syndrome in children: Two recent cases. Can J Infect Dis. 2003;14(6):339–43. doi: 10.1155/2003/219027.
  49. Chesnaye N, Bonthuis M, Schaefer F, Groothoff JW, Verrina E, Heaf JG, Jankauskiene A, Lukosiene V, Molchanova EA, Mota C, Peco-Antić A, Ratsch IM, Bjerre A, Roussinov DL, Sukalo A, Topaloglu R, Van Hoeck K, Zagozdzon I, Jager KJ, Van Stralen KJ; ESPN/ERA-EDTA registry. Demographics of paediatric renal replacement therapy in Europe: a report of the ESPN/ERA-EDTA registry. Pediatr Nephrol. 2014;29(12):2403–10. doi: 10.1007/s00467-014-2884-6.
  50. Grisaru S, Midgley JP, Hamiwka LA, Wade AW, Samuel SM. Diarrhea-associated hemolytic uremic syndrome in southern Alberta: A longterm single-centre experience. Paediatr Child Health. 2011;16(6):337–40. doi: 10.1093/pch/16.6.337.
  51. Robitaille P, Clermont MJ, Mérouani A, Phan V, Lapeyraque AL. Hemolytic uremic syndrome: late renal injury and changing incidence – a single centre experience in Canada. Scientifica (Cairo). 2012;2012:341860. doi: 10.6064/2012/341860.
  52. World Health Organization. Campylobacter [Internet]. Available from: https://www.who.int/foodsafety/areas_work/foodborne-diseases/campylobacter/en/.
  53. World Gastroenterology Organisation. Acute Diarrhea in Adults and Children: A Global Perspective. February 2012 [Internet]. Available from: https://www.worldgastroenterology.org/guidelines/global-guidelines/acute-diarrhea/acute-diarrhea-english.
  54. Макарова ТП, Мрасова ВК, Шакиров ИД, Сенек СА, Осипова НВ. Гемолитико-уремический синдром у детей. Практическая медицина. 2006;(5):18–20.
  55. Keenswijk W, Degraeuwe E, Dhont E, Raes A, Vande Walle J. Hemolytic Uremic Syndrome Associated With Non-Shigatoxin-producing Infectious Agents: Expanding the Shigatoxin Theory. J Pediatr Hematol Oncol. 2019;41(3):e179–81. doi: 10.1097/MPH.0000000000001196.
  56. May T, Gerard A, Voiriot P, Schmit JL, Lion C, Canton P. Entérite à Campylobacter jejuni associée à un syndrome hémolytique et urémique [Campylobacter jejuni enteritis associated with hemolytic-uremic syndrome]. Presse Med. 1986;15(17):803–4. French.
  57. Carter JE, Cimolai N. Hemolytic-uremic syndrome associated with acute Campylobacter upsaliensis gastroenteritis. Nephron. 1996;74(2):489. doi: 10.1159/000189403.
  58. Chamovitz BN, Hartstein AI, Alexander SR, Terry AB, Short P, Katon R. Campylobacter jejuni-associated hemolytic-uremic syndrome in a mother and daughter. Pediatrics. 1983;71(2):253–6.
  59. Soper CP, Sampson SA, Velasco N. Renal thrombotic microangiopathy, campylobacter gastroenteritis and anti-cardiolipin antibody. Nephrol Dial Transplant. 2000;15(8):1261–2. doi: 10.1093/ndt/15.8.1261-a.
  60. Jenssen GR, Vold L, Hovland E, Bangstad HJ, Nygård K, Bjerre A. Clinical features, therapeutic interventions and long-term aspects of hemolytic-uremic syndrome in Norwegian children: a nationwide retrospective study from 1999–2008. BMC Infect Dis. 2016;16:285. doi: 10.1186/s12879-016-1627-7.
  61. Bowen EE, Hangartner R, Macdougall I. Campylobacter-Associated Hemolytic Uremic Syndrome Associated with Pulmonary-Renal Syndrome. J Gen Intern Med. 2016;31(3):353–6. doi: 10.1007/s11606-015-3403-6.
  62. Smith JL, Gunther Iv NW. Commentary: Campylobacter and Hemolytic Uremic Syndrome. Foodborne Pathog Dis. 2019;16(2):90–3. doi: 10.1089/fpd.2018.2513.
  63. Шуляк БФ. Энтерогеморрагические штаммы E. Coli: обзор. Альманах клинической медицины. 2011;25:72–6.
  64. Frank C, Werber D, Cramer JP, Askar M, Faber M, an der Heiden M, Bernard H, Fruth A, Prager R, Spode A, Wadl M, Zoufaly A, Jordan S, Kemper MJ, Follin P, Müller L, King LA, Rosner B, Buchholz U, Stark K, Krause G; HUS Investigation Team. Epidemic profile of Shiga-toxin-producing Escherichia coli O104:H4 outbreak in Germany. N Engl J Med. 2011;365(19):1771–80. doi: 10.1056/NEJMoa1106483.
  65. Cheng J, Yu H, Lau K, Huang S, Chokhawala HA, Li Y, Tiwari VK, Chen X. Multifunctionality of Campylobacter jejuni sialyltransferase CstII: characterization of GD3/GT3 oligosaccharide synthase, GD3 oligosaccharide sialidase, and trans-sialidase activities. Version 2. Glycobiology. 2008;18(9):686–97. doi: 10.1093/glycob/cwn047.
  66. Vincent JL, Castro P, Hunt BJ, Jörres A, Praga M, Rojas-Suarez J, Watanabe E. Thrombocytopenia in the ICU: disseminated intravascular coagulation and thrombotic microangiopathies – what intensivists need to know. Crit Care. 2018;22(1):158. doi: 10.1186/s13054-018-2073-2.
  67. Краснова ЕИ, Гайнц ОВ, Лоскутова СА, Васюнин АВ. Гемолитико-уремический синдром при острых кишечных инфекциях у детей. Детские инфекции. 2011;10(2):63–7.
  68. Ajene AN, Fischer Walker CL, Black RE. Enteric pathogens and reactive arthritis: a systematic review of Campylobacter, salmonella and Shigella-associated reactive arthritis. J Health Popul Nutr. 2013;31(3):299–307. doi: 10.3329/jhpn.v31i3.16515.
  69. Dua K, Banerjee A. Guillain-Barré syndrome: a review. Br J Hosp Med (Lond). 2010;71(9):495–8. doi: 10.12968/hmed.2010.71.9.78159.
  70. Winer JB. Guillain-Barré syndrome: clinical variants and their pathogenesis. J Neuroimmunol. 2011;231(1–2):70–2. doi: 10.1016/j.jneuroim.2010.09.017.

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2020 Karpovich G.S., Krasnova E.I., Vasyunin A.V., Komissarova T.V., Enivatova L.I., Gaynts O.V.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies