Could plasma based therapies still be considered in selected cases with atypical hemolytic uremic syndrome?

Background. Atypical hemolytic uremic syndrome (aHUS) occurs due to defective regulation of the alternative complement pathway (ACP) on vascular endothelial cells. Plasma based therapy (PT) was the mainstay of the treatment for aHUS for many years until the introduction of therapies targeting blockage of the complement system. The aim of this study was to evaluate patients with aHUS who had been treated with plasma based therapies alone. Methods. The outcomes of seven genetically confirmed aHUS patients (2 girls, 5 males) were evaluated by means of clinical presentation, response to plasma therapy, course of the disease during the follow-up period and last status. Results. The median age of the patients at admission was 6.7 years (IQR 0.7-7.8). Three patients received plasma exchange therapy and the other four patients were treated with plasma infusions. One patient was lost to follow-up after one year; the median duration of follow-up for other patients was 3.7 years (IQR 2.7-6.5). During the follow up, two patients from our historical records when complement blocking therapies had not been in clinical use yet in Turkey, underwent kidney transplantation. One transplant patient experienced an acute rejection episode without graft loss. The remaining five patients had a glomerular filtration rate of more than 90 ml/min./1.73 m 2 at the last visit. Conclusion. Although we had a relatively small patient population, our findings indicate that PT might still be considered in selected patients particularly in countries where complement blocking therapies are difficult to reach due to their unavailability or costs that are not covered by the health care systems.

___

1. Ruggenenti P, Noris M, Remuzzi G. Thrombotic microangiopathy, hemolytic uremic syndrome, and thrombotic thrombocytopenic purpura. Kidney Int 2001; 60: 831-846. https://doi.org/10.1046/j.1523- 1755.2001.060003831.x

2. Loirat C, Fakhouri F, Ariceta G, et al; HUS International. An international consensus approach to the management of atypical hemolytic uremic syndrome in children. Pediatr Nephrol 2016; 31: 15- 39. https://doi.org/10.1007/s00467-015-3076-8

3. Kavanagh D, Goodship TH, Richards A. Atypical hemolytic uremic syndrome. Semin Nephrol 2013; 33:508-530. https://doi.org/10.1016/j. semnephrol.2013.08.003

4. Ozaltin F, Li B, Rauhauser A, et al. DGKE variants cause a glomerular microangiopathy that mimics membranoproliferative GN. J Am Soc Nephrol 2013; 24: 377-384. https://doi.org/10.1681/ASN.2012090903

5. Bu F, Maga T, Meyer NC, et al. Comprehensive genetic analysis of complement and coagulation genes in atypical hemolytic uremic syndrome. J Am Soc Nephrol 2014; 25: 55-64. https://doi.org/10.1681/ ASN.2013050453

6. Ariceta G, Besbas N, Johnson S, et al; European Paediatric Study Group for HUS. Guideline for the investigation and initial therapy of diarrhea- negative hemolytic uremic syndrome. Pediatr Nephrol 2009; 24: 687-696. https://doi.org/10.1007/ s00467-008-0964-1

7. Loirat C, Garnier A, Sellier-Leclerc AL, Kwon T. Plasmatherapy in atypical hemolytic uremic syndrome. Semin Thromb Hemost 2010; 36: 673-681. https://doi.org/10.1055/s-0030-1262890

8. Besbas N, Gulhan B, Soylemezoglu O, et al. Turkish pediatric atypical hemolytic uremic syndrome registry: initial analysis of 146 patients. BMC Nephrol 2017; 18: 6. https://doi.org/10.1186/s12882- 016-0420-6

9. Schwartz GJ, Muñoz A, Schneider MF, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol 2009; 20: 629-637. https://doi. org/10.1681/ASN.2008030287

10. Hogg RJ, Portman RJ, Milliner D, Lemley KV, Eddy A, Ingelfinger J. Evaluation and management of proteinuria and nephrotic syndrome in children: recommendations from a pediatric nephrology panel established at the National Kidney Foundation conference on proteinuria, albuminuria, risk, assessment, detection, and elimination (PARADE). Pediatrics 2000; 105: 1242-1249. https://doi. org/10.1542/peds.105.6.1242

11. Inker LA, Astor BC, Fox CH, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis 2014; 63:713-735. https://doi. org/10.1053/j.ajkd.2014.01.416

12. Bukowski RM, King JW, Hewlett JS. Plasmapheresis in the treatment of thrombotic thrombocytopenic purpura. Blood 1977; 50: 413-417. https://doi. org/10.1182/blood.V50.3.413.413

13. Noris M, Caprioli J, Bresin E, 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- 1859. https://doi.org/10.2215/CJN.02210310

14. Waters AM, Licht C. aHUS caused by complement dysregulation: new therapies on the horizon. Pediatr Nephrol 2011; 26: 41-57. https://doi.org/10.1007/ s00467-010-1556-4

15. Gruppo RA, Rother RP. Eculizumab for congenital atypical hemolytic-uremic syndrome. N Engl J Med 2009; 360: 544-546. https://doi.org/10.1056/ NEJMc0809959

16. Nürnberger J, Philipp T, Witzke O, et al. Eculizumab for atypical hemolytic-uremic syndrome N Engl J Med 2009; 360: 542-544. https://doi.org/10.1056/ NEJMc0808527

17. Schaefer F, Ardissino G, Ariceta G, et al; Global aHUS Registry. Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome. Kidney Int 2018; 94: 408-418. https://doi. org/10.1016/j.kint.2018.02.029

18. Gurjar BS, Manikanta Sriharsha T, Bhasym A, et al. Characterization of genetic predisposition and autoantibody profile in atypical haemolytic-uraemic syndrome. Immunology 2018; 154: 663-672. https:// doi.org/10.1111/imm.12916

19. Sellier-Leclerc AL, Fremeaux-Bacchi V, Dragon- Durey MA, et al; French Society of Pediatric Nephrology. Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol 2007; 18: 2392-2400. https://doi.org/10.1681/ ASN.2006080811

20. Fremeaux-Bacchi V, Fakhouri F, Garnier A, 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: 554-562. https://doi.org/10.2215/CJN.04760512

21. Davin JC, Olie KH, Verlaak R, et al. Complement factor H-associated atypical hemolytic uremic syndrome in monozygotic twins: concordant presentation, discordant response to treatment. Am J Kidney Dis 2006; 47: e27-e30. https://doi. org/10.1053/j.ajkd.2005.11.007

22. Lemaire M, Frémeaux-Bacchi V, Schaefer F, et al. Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet 2013; 45: 531-536. https://doi.org/10.1038/ng.2590

23. Azukaitis K, Simkova E, Majid MA, et al. The phenotypic spectrum of nephropathies associated with mutations in diacylglycerol kinase ε. J Am Soc Nephrol 2017; 28: 3066-3075. https://doi.org/10.1681/ ASN.2017010031

24. Loirat C, Saland J, Bitzan M. Management of hemolytic uremic syndrome. Presse Med 2012; 41(3 Pt 2): e115-e135. https://doi.org/10.1016/j. lpm.2011.11.013

25. Fujisawa M, Kato H, Yoshida Y, et al. Clinical characteristics and genetic backgrounds of Japanese patients with atypical hemolytic uremic syndrome. Clin Exp Nephrol 2018; 22: 1088-1099. https://doi. org/10.1007/s10157-018-1549-3

26. Caprioli J, Noris M, Brioschi S, et al; International Registry of Recurrent and Familial HUS/TTP. Genetics of HUS: the impact of MCP, CFH, and IF mutations on clinical presentation, response to treatment, and outcome. Blood 2006; 108: 1267-1279. https://doi.org/10.1182/blood-2005-10-007252

27. Reid VL, Mullan A, Erwig LP. Rapid recovery of membrane cofactor protein (MCP; CD46) associated atypical haemolytic uraemic syndrome with plasma exchange. BMJ Case Rep 2013; 2013: bcr2013200980. https://doi.org/10.1136/bcr-2013-200980

28. Marini SC, Gomes M, Guilherme R, et al. Atypical hemolytic-uremic syndrome: recurrent phenotypic expression of a patient with MCP gene mutation combined with risk haplotypes. Blood Coagul Fibrinolysis 2019; 30: 68-70. https://doi.org/10.1097/ MBC.0000000000000793

29. National Institute for Health and Care Excellence. National Institute for Health and Care Excellence guidance: eculizumab for treating atypical haemolytic uraemic syndrome. London: NICE, 2015. Available at: https://www.nice.org.uk/ guidance/ hst1/chapter/7-Recommendations-for-further- research (Accessed on November 15th, 2020).

30. Ardissino G, Testa S, Possenti I, et al. Discontinuation of eculizumab maintenance treatment for atypical hemolytic uremic syndrome: a report of 10 cases. Am J Kidney Dis 2014; 64: 633-637. https://doi. org/10.1053/j.ajkd.2014.01.434

31. Wijnsma KL, Duineveld C, Volokhina EB, van den Heuvel LP, van de Kar NCAJ, Wetzels JFM. Safety and effectiveness of restrictive eculizumab treatment in atypical haemolytic uremic syndrome. Nephrol Dial Transplant 2018; 33: 635-645. https:// doi.org/10.1093/ndt/gfx196
Turkish Journal of Pediatrics-Cover
  • ISSN: 0041-4301
  • Yayın Aralığı: Yılda 6 Sayı
  • Başlangıç: 1958
  • Yayıncı: Hacettepe Üniversitesi Çocuk Sağlığı Enstitüsü Müdürlüğü
Sayıdaki Diğer Makaleler

Clinical follow-up of children with high vitamin B12 values: should we worry?

Davut ALBAYRAK, Canan ALBAYRAK

The relationship between immature platelet fraction and severity of acute bronchiolitis

Murat DOĞAN, Mehmet KÖSE, Mehmet Adnan ÖZTÜRK, Melih HANGÜL, Hümeyra ASLANER

Investigation of immunity against Bordetella pertussis in pregnant women and an overview of the vaccination schedule in Turkey

Serdar GÜL, Cemile SÖNMEZ, Gökçe AYVAZ, Selçuk KILIÇ

Short and long term side effect of colistin treatment in preterm infants

Sadık YURTTUTAN, Burcu Cantay ATALAY

The rare reason of pain in hip girdle: Mucolipidosis type 3 gamma

Abdulkerim KOLKIRAN, Beren KARAOSMANOĞLU, Zihni Ekim TAŞKIRAN, Pelin Özlem ŞİMŞEK KİPER, Gülen Eda UTİNE

Thiol / disulfide balance and oxidative stress parameters in pediatric patients diagnosed with acute and chronic idiopathic thrombocytopenic purpura

Yeter DÜZENLİ KAR, Zeynep Canan ÖZDEMİR, Özcan BÖR

Covid-19 in a patient with Familial Hemophagocytic Lymphohistiocytosis in children

V. Hülya ÜZEL, Kamil YILMAZ

Tuberculosis risk in the biologic era: tuberculin skin test conversion rates in children with rheumatologic diseases

Canan ÖZLÜ, Serkan TÜRKUÇAR, Hatice KARAOĞLU ASRAK, Hatice Adıgüzel DÜNDAR, Şevket Erbil ÜNSAL, Nurşen BELET

Hematopoietic stem cell transplantation complicated with EBV associated hemophagocytic lymphohistiocytosis in a patient with DOCK2 deficiency

Elif Soyak AYTEKİN, Deniz ÇAĞDAŞ, Çağman TAN, Büşranur ÇAVDARLI, Işıl BİLGİÇ, İlhan TEZCAN

A case of pediatric psoriasis achieving remission after allogenic bone marrow transplantation

Dilara GÜLER, Gülhan GÜREL, Gülsüm Şeyma YALÇIN, İbrahim EKER, İrem Nur DURUSU, Çiğdem ÖZDEMİR, Özge VURAL