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Journal Details
License
Format
Journal
First Published
30 Mar 2015
Publication timeframe
4 times per year
Languages
English
access type Open Access

Discontinuation of Eculizumab treatment after hematological remission in patients with atypical and drug-induced hemolytic uremic syndrome

Published Online: 26 Aug 2021
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Received: 22 Jun 2021
Journal Details
License
Format
Journal
First Published
30 Mar 2015
Publication timeframe
4 times per year
Languages
English
Abstract

Introduction: To evaluate the effect of therapeutic plasma exchange(TPE) and eculizumab on hematological and renal survival in atypical hemolytic uremic syndrome(aHUS). Additionally, to examine the reliability of discontinuation of eculizumab treatment.

Methods: This was an observational and retrospective study of 18 patients diagnosed with aHUS.

Results: The median age of the study population was 30(22-66) years. Four of 18 patients achieved hematological remission with the TPE alone. However, one patient in the died after three sessions of TPE. Eculizumab was used in 13 patients and no death was observed. One year after treatment, improved kidney function was observed in 2 of 3(66%) patients for TPE and 5 of 9(56%) patients for Eculizumab. We discontinued eculizumab treatment in 9 patients. One of the patients who had a C3 gene mutation experienced disease relapse after Eculizumab discontinuation. None of the patients who had drug associated aHUS, developed disease relapse after Eculizumab discontinuation.

Conclusion: Eculizumab treatment is a life-saving therapy in aHUS. Treatment discontinuation may be considered at least six months after hematologic remission in patients who had stable renal function or no expectancy for renal survival. Moreover, drug-associated cases seem to tend not to develop disease relapse in the long term.

Keywords

1. CAO M, LEITE BN, FERREIRO T, CALVO M, FERNANDEZ C, ALONSO A, et al., Eculizumab modifies outcomes in adults with atypical hemolytic uremic syndrome with acute kidney injury. Am J Nephrol 2018; 48: p. 225-233.Search in Google Scholar

2. NORIS M and REMUZZI G, Atypical hemolytic–uremic syndrome. N Engl J Med 2009; 361: p. 1676-1687.Search in Google Scholar

3. 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. Nefrología (English Edition) 2015; 35: p. 421-447.Search in Google Scholar

4. KATO H, MIYAKAWA Y, HIDAKA Y, INOUE N, ITO S, KAGAMI S, et al., Safety and effectiveness of Eculizumab for adult patients with atypical hemolytic–uremic syndrome in Japan: interim analysis of post-marketing surveillance. Clin Exp Nephrol. 2019; 23: p. 65-75.Search in Google Scholar

5. RAINA R, GREWAL MK, RADHAKRISHNAN Y, TATINENI V, DECOY M, BURKE LL, et al., Optimal management of atypical hemolytic uremic disease: challenges and solutions. Int J Nephrol Renovasc Dis 2019; 12: p. 183.Search in Google Scholar

6. KRISHNAPPA V, GUPTA M, ELRIFAI M, MOFTAKHAR B, ENSLEY MJ, VACHHARAJANI TJ, et al., Atypical hemolytic uremic syndrome: a meta-analysis of case reports confirms the prevalence of genetic mutations and the shift of treatment regimens. Ther Apher Dial 2018; 22: p. 178-188.Search in Google Scholar

7. LEE H, KANG E, KANG HG, KIM YH, KIM JS, KIM H-J, et al., Consensus regarding diagnosis and management of atypical hemolytic uremic syndrome. Korean J Intern Med. 2020; 35: p. 25-40.Search in Google Scholar

8. KHWAJA A, KDIGO clinical practice guidelines for acute kidney injury. Nephron Clin Pract. 2012; 120: p. c179-c184.Search in Google Scholar

9. CAMPISTOL JM, ARIAS M, ARICETA G, BLASCO M, ESPINOSA M, GRINYÓ JM, et al., An update for atypical haemolytic uraemic syndrome: diagnosis and treatment. A consensus document. Nefrologia.2015;35(5):421-447Search in Google Scholar

10. FREMEAUX-BACCHI V, FAKHOURI F, GARNIER A, BIENAIMÉ F, DRAGON-DUREY M-A, 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: p. 554-562.Search in Google Scholar

11. 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: p. 1844-1859.Search in Google Scholar

12. JOKIRANTA TS, HUS and atypical HUS. Blood, T 2017; 129: p. 2847-2856.Search in Google Scholar

13. LEGENDRE CM, LICHT C, MUUS P, GREENBAUM L, BABU S, BEDROSIAN C, et al., Terminal complement inhibitor eculizumab in atypical hemolytic–uremic syndrome. N Engl J Med. 2013; 368: p. 2169-2181.Search in Google Scholar

14. 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: p. 539-551.Search in Google Scholar

15. OSBORNE AJ, BRENO M, BORSA NG, BU F, FRÉMEAUX-BACCHI V, GALE DP, et al., Statistical Validation of Rare Complement Variants Provides Insights into the Molecular Basis of Atypical Hemolytic Uremic Syndrome and C3 Glomerulopathy. J Immunol 2018; 200: p. 2464-2478.Search in Google Scholar

16. CAVERO T, RABASCO C, LÓPEZ A, ROMÁN E, ÁVILA A, SEVILLANO Á, et al., Eculizumab in secondary atypical haemolytic uraemic syndrome. Nephrol Dial Transplant. 2017; 32: p. 466-474.Search in Google Scholar

17. MERRILL SA, BRITTINGHAM ZD, YUAN X, MOLITERNO AR, SPERATI CJ, and BRODSKY RA, Eculizumab cessation in atypical hemolytic uremic syndrome. Blood 2017; 130: p. 368-372.Search in Google Scholar

18. 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: p. 50-59.Search in Google Scholar

19. ARDISSINO G, POSSENTI I, TEL F, TESTA S, SALARDI S, and LADISA V, Discontinuation of eculizumab treatment in atypical hemolytic uremic syndrome: an update. Am J Kidney Dis. 2015; 66: p. 172-173.Search in Google Scholar

20. OLSON SR, LU E, SULPIZIO E, SHATZEL JJ, RUEDA JF, and DELOUGHERY TG, When to stop Eculizumab in complement-mediated thrombotic microangiopathies. Am J Nephrol. 2018; 48: p. 96-107.Search in Google Scholar

21. FREMEAUX-BACCHI V, MOULTON EA, KAVANAGH D, DRAGON-DUREY M-A, BLOUIN J, CAUDY A, et al., Genetic and functional analyses of membrane cofactor protein (CD46) mutations in atypical hemolytic uremic syndrome. J Am Soc Nephrol. 2006; 17: p. 2017-2025.Search in Google Scholar

22. WIJNSMA KL, DUINEVELD C, VOLOKHINA EB, VAN DEN HEUVEL LP, VAN DE KAR NC, and WETZELS JF, Safety and effectiveness of restrictive eculizumab treatment in atypical haemolytic uremic syndrome. Nephrol Dial Transplant 2018; 33: p. 635-645.Search in Google Scholar

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