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Long-Term Outcomes of Patients with Atypical Hemolytic Uremic Syndrome

Year 2023, Volume: 2 Issue: 2, 78 - 83, 19.06.2023

Pelin Ertan Esra Nagehan Akyol Onder Afig Hüseyinov Berdeli

https://doi.org/10.57221/izmirtip.1271012

Abstract

Aim: Hemolytic uremic syndrome (HUS) is the clinical triad of anemia, thrombocytopenia and acute renal injury. Atypical hemolytic uremic syndrome (aHUS) is a rare disease of alternative complement pathways. It is aimed to evaluate long-term follow-up of patients with aHUS in the present study. Materials and methods: Eleven children diagnosed with aHUS were retrospectively evaluated. Demographic, clinical, and laboratory data and treatment details were reported. Results: A total of 11 patients were enrolled in the study. The mean age of patients at aHUS onset was 2.9±6 years. The mean follow-up time was 72 ± 4 months All patients had renal involvement. Extrarenal manifestations of aHUS were present in four patients. All patients had eculizumab treatment. Conclusion: Our study insight into diagnosing and managing aHUS, a very rare disease, in our pediatric patients. Genetic testing is used to improve the diagnosis of aHUS. We demonstrated the long-term efficacy and safety of eculizumab in our aHUS patients. Further studies are needed to determine the optimal time for discontinuation of eculizumab treatment.

Keywords

Atypical hemolytic uremic syndrome children complement pathway eculizumab

Thanks

Medical writing was supported by Alexion Pharma Turkey.

References

  • Referans1. Raina R, Krishnappa V, Blaha T, Kann T, Hein W, Burke L et al. Atypical hemolytic-uremic syndrome: An update on pathophysiology, diagnosis, and treatment. Ther Apher Dial. 2019;23:4-21.
  • Referans2. 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.
  • Referans3. Loirat C, Fakhouri F, Ariceta G, Besbas N, Bitzan M, Bjerre A et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2016;31:15–39.
  • Referans4. Zimmerhackl LB, Besbas N, Jungraithmayr T, Van De Kar N, Karch H, Karpman D et al. Epidemiology, clinical presentation, and pathophysiology of atypical and recurrent hemolytic uremic syndrome. Semin Thromb Hemost. 2006;32:113-20.
  • Referans5. Valoti E, Alberti M, Iatropoulos P, Piras R, Mele C, Breno M et al. Rare functional variants in complement genes and anti-FH autoantibodies-associated aHUS. Front Immunol. 2019;10:853. Referans6. Campistol JM, Arias M, Ariceta G, Blasco M, Espinosa L, Espinosa M et al. An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia. 2015;35:421-47. Referans7. Dixon BP, Gruppo RA. Atypical hemolytic uremic syndrome. Pediatr Clin North Am. 2018;65:509-25.
  • Referans8. Schaefer F, Ardissino G, Ariceta G, Fakhouri F, Scully M, Isbel N et al. Global aHUS Registry. Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome. Kidney Int. 2018; 94: 408-18.
  • Referans9. Le Clech A, Simon-Tillaux N, Provôt F, Delmas Y, Vieira-Martins P, Limou S et al. Atypical and secondary hemolytic uremic syndromes have a distinct presentation and no common genetic risk factors. Kidney Int. 2019;95:1443-52.
  • Referans10. Fakhouri F, Fila M, Provôt F, Delmas Y, Barbet C, Châtelet V et al. Pathogenic variants in complement genes and risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation. Clin J Am Soc Nephrol. 2017;12:50–9.
  • Referans11. Fakhouri F, Hourmant M, Campistol JM, Cataland SR, Espinosa M, Gaber AO et al. Terminal complement inhibitor eculizumab in adult patients with atypical hemolytic uremic syndrome: A single-arm, Open-Label Trial. Am J Kidney Dis. 2016;68:84-93. Referans12. Goodship TH, Cook HT, Fakhouri F, Fervenza FC, Frémeaux-Bacchi V, Kavanagh D et al. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. Kidney Int. 2017; 91: 539-51.
  • Referans13. Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clinrate in infants, children, and adolescents. Pediatr Clin North Am. 1987;34:571-90.
  • Referans14. Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int. 2007;71:1028-35.
  • Referans15. Sa´nchez-Corral P, Melgosa M. Advances in understanding the aetiology of atypical haemolytic uraemic syndrome. Br J Haematol. 2010;150:529-42. Referans16. Fakhouri F, Zuber J, Frémeaux-Bacchi V, Loirat C. Haemolytic uraemic syndrome. Lancet. 2017;390 (10095):681-96.
  • Referans17. Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaimé F, Dragon-Durey MA, 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. 2013;8:554–62.
  • Referans18. Geerdink LM, Westra D, Van Wijk JAE, Dorresteijn EM, Lilien MR, Davin JC et al. Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics. Pediatr Nephrol. 2012,27:1283-91.
  • Referans19. Besbas N, Gulhan B, Soylemezoglu O, Ozcakar ZB, Korkmaz E, Hayran M et al. Turkish pediatric atypical hemolytic uremic syndrome registry: initial analysis of 146 patients. BMC Nephrol. 2017;18:6.
  • Referans20. Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol. 2010;5:1844–59.
  • Referans21. Maximiano C, Silva A, Duro I, Branco T, Correia-Costa L, Teixeira A et al. Genetic atypical hemolytic uremic syndrome in children: a 20-year experience from a tertiary center. J Bras Nefrol. 2021:S0101-28002021005042302.
  • Referans22. Sinha A, Gulati A, Saini S, Blanc C, Gupta A, Gurjar BS 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.
  • Referans23. Lee JM, Park YS, Lee JH, Park SJ, Shin JI, Park YH et al. Atypical hemolytic uremic syndrome: Korean pediatric series. Pediatr Int. 2015;57:431-8.
  • Referans24. Caprioli J, Bettinaglio P, Zipfel PF, Amadei B, Daina E, Gamba S et al. Italian Registry of Familial and Recurrent HUS/TTP. 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;12:297-307.
  • Referans25. Neumann HPH, Salzmann M, Bohnert-Iwan B, Mannuelian T, Skerka C, Lenk D et al. Haemolytic uraemic syndrome and mutations of the factor H gene: a registry-based study of German speaking countries. J Med Genet. 2003;40:676-8.
  • Referans26. Macia M, de Alvaro Moreno F, Dutt T, Fehrman I, Hadaya K, Gasteyger C et al. Current evidence on the discontinuation of eculizumab in patients with atypical haemolytic uraemic syndrome. Clin Kidney J. 2017;10: 310-9.
  • Referans27. Fakhouri F, Fila M, Provot F, Delmas Y, Barbet C, Châtelet V et al. Pathogenic variants in complement genes and risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation. Clin J Am Soc Nephrol. 2017;12:50-9.
  • Referans28. Baskin E, Fidan K, Gulhan B, Gulleroglu K, Canpolat N, Yilmaz A et al. Eculizumab treatment and discontinuation in pediatric patients with atypical hemolytic uremic syndrome: a multicentric retrospective study. J Nephrol. 2022;35:1213-22.

Atipik Hemolitik Üremik Sendromlu Hastaların Uzun Dönem Sonuçları

Year 2023, Volume: 2 Issue: 2, 78 - 83, 19.06.2023

Pelin Ertan Esra Nagehan Akyol Onder Afig Hüseyinov Berdeli

https://doi.org/10.57221/izmirtip.1271012

Abstract

Amaç: Hemolitik üremik sendrom (HÜS), anemi, trombositopeni ve akut böbrek hasarının klinik üçlüsünden oluşur. Atipik hemolitik üremik sendrom (aHÜS), alternatif kompleman yollarının nadir görülen bir hastalığıdır. Bu çalışmada, aHÜS'lü hastaların uzun dönem takiplerinin değerlendirilmesi amaçlandı. Gereç ve Yöntemler: Atipik hemolitik üremik sendrom tanısı alan 11 çocuk retrospektif olarak değerlendirildi. Demografik, klinik ve laboratuvar verileri ve tedavi detayları rapor edildi. Bulgular: Çalışmaya toplam 11 hasta dahil edildi. aHÜS başlangıçlı hastaların ortalama yaşı 2,9±6 idi. Ortalama takip süresi 72 ± 4 aydı. Tüm hastalarda böbrek tutulumu vardı. aHÜS'ün böbrek dışı belirtileri dört hastada mevcuttu. Tüm hastalara ekulizumab tedavisi uygulandı. Sonuç: Çalışmamız pediatrik hastalarımızda çok nadir görülen bir hastalık olan aHÜS'ün tanı ve tedavisine ışık tutmaktadır. aHÜS tanısını güçlendirmek için genetik testlere ihtiyaç vardır. aHÜS hastalarımızda ekulizumab'ın uzun vadeli etkinliğini ve güvenliliğini gösterdik. Ekulizumab tedavisinin kesilmesi için en uygun zamanı belirlemek için daha ileri çalışmalara ihtiyaç vardır.

Keywords

Atipik Hemolitik Üremik Sendrom çocuk Ekulizumab kompleman sistemi

References

  • Referans1. Raina R, Krishnappa V, Blaha T, Kann T, Hein W, Burke L et al. Atypical hemolytic-uremic syndrome: An update on pathophysiology, diagnosis, and treatment. Ther Apher Dial. 2019;23:4-21.
  • Referans2. 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.
  • Referans3. Loirat C, Fakhouri F, Ariceta G, Besbas N, Bitzan M, Bjerre A et al. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol. 2016;31:15–39.
  • Referans4. Zimmerhackl LB, Besbas N, Jungraithmayr T, Van De Kar N, Karch H, Karpman D et al. Epidemiology, clinical presentation, and pathophysiology of atypical and recurrent hemolytic uremic syndrome. Semin Thromb Hemost. 2006;32:113-20.
  • Referans5. Valoti E, Alberti M, Iatropoulos P, Piras R, Mele C, Breno M et al. Rare functional variants in complement genes and anti-FH autoantibodies-associated aHUS. Front Immunol. 2019;10:853. Referans6. Campistol JM, Arias M, Ariceta G, Blasco M, Espinosa L, Espinosa M et al. An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia. 2015;35:421-47. Referans7. Dixon BP, Gruppo RA. Atypical hemolytic uremic syndrome. Pediatr Clin North Am. 2018;65:509-25.
  • Referans8. Schaefer F, Ardissino G, Ariceta G, Fakhouri F, Scully M, Isbel N et al. Global aHUS Registry. Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome. Kidney Int. 2018; 94: 408-18.
  • Referans9. Le Clech A, Simon-Tillaux N, Provôt F, Delmas Y, Vieira-Martins P, Limou S et al. Atypical and secondary hemolytic uremic syndromes have a distinct presentation and no common genetic risk factors. Kidney Int. 2019;95:1443-52.
  • Referans10. Fakhouri F, Fila M, Provôt F, Delmas Y, Barbet C, Châtelet V et al. Pathogenic variants in complement genes and risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation. Clin J Am Soc Nephrol. 2017;12:50–9.
  • Referans11. Fakhouri F, Hourmant M, Campistol JM, Cataland SR, Espinosa M, Gaber AO et al. Terminal complement inhibitor eculizumab in adult patients with atypical hemolytic uremic syndrome: A single-arm, Open-Label Trial. Am J Kidney Dis. 2016;68:84-93. Referans12. Goodship TH, Cook HT, Fakhouri F, Fervenza FC, Frémeaux-Bacchi V, Kavanagh D et al. Atypical hemolytic uremic syndrome and C3 glomerulopathy: conclusions from a "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference. Kidney Int. 2017; 91: 539-51.
  • Referans13. Schwartz GJ, Brion LP, Spitzer A. The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children, and adolescents. Pediatr Clinrate in infants, children, and adolescents. Pediatr Clin North Am. 1987;34:571-90.
  • Referans14. Akcan-Arikan A, Zappitelli M, Loftis LL, Washburn KK, Jefferson LS, Goldstein SL. Modified RIFLE criteria in critically ill children with acute kidney injury. Kidney Int. 2007;71:1028-35.
  • Referans15. Sa´nchez-Corral P, Melgosa M. Advances in understanding the aetiology of atypical haemolytic uraemic syndrome. Br J Haematol. 2010;150:529-42. Referans16. Fakhouri F, Zuber J, Frémeaux-Bacchi V, Loirat C. Haemolytic uraemic syndrome. Lancet. 2017;390 (10095):681-96.
  • Referans17. Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaimé F, Dragon-Durey MA, 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. 2013;8:554–62.
  • Referans18. Geerdink LM, Westra D, Van Wijk JAE, Dorresteijn EM, Lilien MR, Davin JC et al. Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics. Pediatr Nephrol. 2012,27:1283-91.
  • Referans19. Besbas N, Gulhan B, Soylemezoglu O, Ozcakar ZB, Korkmaz E, Hayran M et al. Turkish pediatric atypical hemolytic uremic syndrome registry: initial analysis of 146 patients. BMC Nephrol. 2017;18:6.
  • Referans20. Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S et al. Relative role of genetic complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol. 2010;5:1844–59.
  • Referans21. Maximiano C, Silva A, Duro I, Branco T, Correia-Costa L, Teixeira A et al. Genetic atypical hemolytic uremic syndrome in children: a 20-year experience from a tertiary center. J Bras Nefrol. 2021:S0101-28002021005042302.
  • Referans22. Sinha A, Gulati A, Saini S, Blanc C, Gupta A, Gurjar BS 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.
  • Referans23. Lee JM, Park YS, Lee JH, Park SJ, Shin JI, Park YH et al. Atypical hemolytic uremic syndrome: Korean pediatric series. Pediatr Int. 2015;57:431-8.
  • Referans24. Caprioli J, Bettinaglio P, Zipfel PF, Amadei B, Daina E, Gamba S et al. Italian Registry of Familial and Recurrent HUS/TTP. 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;12:297-307.
  • Referans25. Neumann HPH, Salzmann M, Bohnert-Iwan B, Mannuelian T, Skerka C, Lenk D et al. Haemolytic uraemic syndrome and mutations of the factor H gene: a registry-based study of German speaking countries. J Med Genet. 2003;40:676-8.
  • Referans26. Macia M, de Alvaro Moreno F, Dutt T, Fehrman I, Hadaya K, Gasteyger C et al. Current evidence on the discontinuation of eculizumab in patients with atypical haemolytic uraemic syndrome. Clin Kidney J. 2017;10: 310-9.
  • Referans27. Fakhouri F, Fila M, Provot F, Delmas Y, Barbet C, Châtelet V et al. Pathogenic variants in complement genes and risk of atypical hemolytic uremic syndrome relapse after eculizumab discontinuation. Clin J Am Soc Nephrol. 2017;12:50-9.
  • Referans28. Baskin E, Fidan K, Gulhan B, Gulleroglu K, Canpolat N, Yilmaz A et al. Eculizumab treatment and discontinuation in pediatric patients with atypical hemolytic uremic syndrome: a multicentric retrospective study. J Nephrol. 2022;35:1213-22.
There are 24 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Articles
Authors

Pelin Ertan 0000-0002-1882-5962

Esra Nagehan Akyol Onder 0000-0003-0321-2204

Afig Hüseyinov Berdeli 0000-0002-4791-8367

Publication Date June 19, 2023
Submission Date March 26, 2023
Published in Issue Year 2023 Volume: 2 Issue: 2

Cite

APA Ertan, P., Akyol Onder, E. N., & Berdeli, A. H. (2023). Long-Term Outcomes of Patients with Atypical Hemolytic Uremic Syndrome. İzmir Tıp Fakültesi Dergisi, 2(2), 78-83. https://doi.org/10.57221/izmirtip.1271012
AMA Ertan P, Akyol Onder EN, Berdeli AH. Long-Term Outcomes of Patients with Atypical Hemolytic Uremic Syndrome. İzmir Tıp Fak. Derg. June 2023;2(2):78-83. doi:10.57221/izmirtip.1271012
Chicago Ertan, Pelin, Esra Nagehan Akyol Onder, and Afig Hüseyinov Berdeli. “Long-Term Outcomes of Patients With Atypical Hemolytic Uremic Syndrome”. İzmir Tıp Fakültesi Dergisi 2, no. 2 (June 2023): 78-83. https://doi.org/10.57221/izmirtip.1271012.
EndNote Ertan P, Akyol Onder EN, Berdeli AH (June 1, 2023) Long-Term Outcomes of Patients with Atypical Hemolytic Uremic Syndrome. İzmir Tıp Fakültesi Dergisi 2 2 78–83.
IEEE P. Ertan, E. N. Akyol Onder, and A. H. Berdeli, “Long-Term Outcomes of Patients with Atypical Hemolytic Uremic Syndrome”, İzmir Tıp Fak. Derg., vol. 2, no. 2, pp. 78–83, 2023, doi: 10.57221/izmirtip.1271012.
ISNAD Ertan, Pelin et al. “Long-Term Outcomes of Patients With Atypical Hemolytic Uremic Syndrome”. İzmir Tıp Fakültesi Dergisi 2/2 (June 2023), 78-83. https://doi.org/10.57221/izmirtip.1271012.
JAMA Ertan P, Akyol Onder EN, Berdeli AH. Long-Term Outcomes of Patients with Atypical Hemolytic Uremic Syndrome. İzmir Tıp Fak. Derg. 2023;2:78–83.
MLA Ertan, Pelin et al. “Long-Term Outcomes of Patients With Atypical Hemolytic Uremic Syndrome”. İzmir Tıp Fakültesi Dergisi, vol. 2, no. 2, 2023, pp. 78-83, doi:10.57221/izmirtip.1271012.
Vancouver Ertan P, Akyol Onder EN, Berdeli AH. Long-Term Outcomes of Patients with Atypical Hemolytic Uremic Syndrome. İzmir Tıp Fak. Derg. 2023;2(2):78-83.
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