Top

Published in:

05-05-2024 | Hemolytic Uremic Syndrome | Original article

Adolescence-onset atypical hemolytic uremic syndrome: is it different from infant-onset?

Authors: Kubra Celegen, Bora Gulhan, Kibriya Fidan, Selcuk Yuksel, Neslihan Yilmaz, Aysun Caltik Yılmaz, Beltinge Demircioğlu Kılıç, Ibrahim Gokce, Aslı Kavaz Tufan, Mukaddes Kalyoncu, Hulya Nalcacıoglu, Sare Gulfem Ozlu, Eda Didem Kurt Sukur, Nur Canpolat, Aysun K. Bayazit, Elif Çomak, Yılmaz Tabel, Sebahat Tulpar, Mehtap Celakil, Kenan Bek, Cengiz Zeybek, Ali Duzova, Zeynep Birsin Özçakar, Rezan Topaloglu, Oguz Soylemezoglu, Fatih Ozaltin

Published in: Clinical and Experimental Nephrology | Issue 10/2024

Abstract

Background

Atypical hemolytic uremic syndrome (aHUS) is a rare, mostly complement-mediated thrombotic microangiopathy. The majority of patients are infants. In contrast to infantile-onset aHUS, the clinical and genetic characteristics of adolescence-onset aHUS have not been sufficiently addressed to date.

Methods

A total of 28 patients (21 girls, 7 boys) who were diagnosed as aHUS between the ages of ≥10 years and <18 years were included in this study. All available data in the Turkish Pediatric aHUS registry were collected and analyzed.

Results

The mean age at diagnosis was 12.8±2.3 years. Extra-renal involvement was noted in 13 patients (46.4%); neurological involvement was the most common (32%). A total of 21 patients (75%) required kidney replacement therapy. Five patients (17.8%) received only plasma therapy and 23 (82%) of the patients received eculizumab. Hematologic remission and renal remission were achieved in 25 (89.3%) and 17 (60.7%) of the patients, respectively. Compared with the infantile-onset aHUS patients, adolescent patients had a lower complete remission rate during the first episode (p = 0.002). Genetic analyses were performed in all and a genetic variant was detected in 39.3% of the patients. The mean follow-up duration was 4.9±2.6 years. At the last visit, adolescent patients had lower eGFR levels (p = 0.03) and higher rates of chronic kidney disease stage 5 when compared to infantile-onset aHUS patients (p = 0.04).

Conclusions

Adolescence-onset aHUS is a rare disease but tends to cause more permanent renal dysfunction than infantile-onset aHUS. These results may modify the management approaches in these patients.

Available only for authorised users

Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaime 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(4):554–62. https://doi.org/10.2215/CJN.04760512.CrossRefPubMedPubMedCentral

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(10):1844–59. https://doi.org/10.2215/CJN.02210310.CrossRefPubMedPubMedCentral

Schaefer F, Ardissino G, Ariceta G, Fakhouri F, Scully M, Isbel N, et al. Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome. Kidney Int. 2018;94(2):408–18. https://doi.org/10.1016/j.kint.2018.02.029.CrossRefPubMed

Feitz WJC, van de Kar N, Orth-Höller D, van den Heuvel L, Licht C. The genetics of atypical hemolytic uremic syndrome. Med Genet Mitteil Berufsver Med Genet. 2018;30(4):400–9. https://doi.org/10.1007/s11825-018-0216-0.CrossRef

Ozaltin F, Li B, Rauhauser A, An SW, Soylemezoglu O, Gonul II, et al. DGKE variants cause a glomerular microangiopathy that mimics membranoproliferative GN. J Am Soc Nephrol JASN. 2013;24(3):377–84. https://doi.org/10.1681/asn.2012090903.CrossRefPubMed

Canpolat N, Liu D, Atayar E, Saygili S, Kara NS, Westfall TA, et al. A splice site mutation in the TSEN2 causes a new syndrome with craniofacial and central nervous system malformations, and atypical hemolytic uremic syndrome. Clin Genet. 2022;101(3):346–58. https://doi.org/10.1111/cge.14105.CrossRefPubMedPubMedCentral

Syed YY. Ravulizumab: a review in atypical haemolytic uraemic syndrome. Drugs. 2021;81(5):587–94. https://doi.org/10.1007/s40265-021-01481-6.CrossRefPubMedPubMedCentral

Licht C, Ardissino G, Ariceta G, Cohen D, Cole JA, Gasteyger C, et al. The global aHUS registry: methodology and initial patient characteristics. BMC Nephrol. 2015;16:207. https://doi.org/10.1186/s12882-015-0195-1.CrossRefPubMedPubMedCentral

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(1):6. https://doi.org/10.1186/s12882-016-0420-6.CrossRefPubMedPubMedCentral

10.

Johnson S, Stojanovic J, Ariceta G, Bitzan M, Besbas N, Frieling M, et al. An audit analysis of a guideline for the investigation and initial therapy of diarrhea negative (atypical) hemolytic uremic syndrome. Pediatr Nephrol. 2014;29(10):1967–78. https://doi.org/10.1007/s00467-014-2817-4.CrossRefPubMed

11.

Cakar N, Ozcakar ZB, Ozaltin F, Koyun M, Celikel Acar B, Bahat E, et al. Atypical hemolytic uremic syndrome in children aged <2 years. Nephron. 2018;139(3):211–8. https://doi.org/10.1159/000487609.CrossRefPubMed

12.

Singh JA, Siddiqi M, Parameshwar P, Chandra-Mouli V. World Health Organization guidance on ethical considerations in planning and reviewing research studies on sexual and reproductive health in adolescents. J Adoles Health. 2019;64(4):427–9. https://doi.org/10.1016/j.jadohealth.2019.01.008.CrossRef

13.

Kellum JA, Lameire N. Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (part 1). Critic Care (London, England). 2013;17(1):204. https://doi.org/10.1186/cc11454.CrossRef

14.

Kaddourah A, Basu RK, Bagshaw SM, Goldstein SL. Epidemiology of acute kidney injury in critically Ill children and young adults. N Engl J Med. 2017;376(1):11–20. https://doi.org/10.1056/NEJMoa1611391.CrossRefPubMed

15.

Bresolin N, Silva C, Halllal A, Toporovski J, Fernandes V, Góes J, et al. Prognosis for children with acute kidney injury in the intensive care unit. Pediatr Nephrol. 2009;24(3):537–44. https://doi.org/10.1007/s00467-008-1054-0.CrossRefPubMed

16.

Tapper D, Tarr P, Avner E, Brandt J, Waldhausen J. Lessons learned in the management of hemolytic uremic syndrome in children. J Pediatr Surg. 1995;30(2):158–63. https://doi.org/10.1016/0022-3468(95)90554-5.CrossRefPubMed

17.

Scully M, Cataland S, Coppo P, de la Rubia J, Friedman KD, Kremer Hovinga J, et al. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost JTH. 2017;15(2):312–22. https://doi.org/10.1111/jth.13571.CrossRefPubMed

18.

Verhave JC, Wetzels JF, van de Kar NC. Novel aspects of atypical haemolytic uraemic syndrome and the role of eculizumab. Nephrol Dial Transplant. 2014;29(Suppl 4):iv131–4. https://doi.org/10.1093/ndt/gfu235.CrossRefPubMed

19.

Schwartz GJ, Muñoz A, Schneider MF, Mak RH, Kaskel F, Warady BA, et al. New equations to estimate GFR in children with CKD. J Am Soc Nephrol JASN. 2009;20(3):629–37. https://doi.org/10.1681/asn.2008030287.CrossRefPubMed

20.

Patel SS, Kimmel PL, Singh A. New clinical practice guidelines for chronic kidney disease: a framework for K/DOQI. Semin Nephrol. 2002;22(6):449–58. https://doi.org/10.1053/snep.2002.35973.CrossRefPubMed

21.

Lurbe E, Agabiti-Rosei E, Cruickshank JK, Dominiczak A, Erdine S, Hirth A, et al. 2016 European society of hypertension guidelines for the management of high blood pressure in children and adolescents. J Hypertens. 2016;34(10):1887–920. https://doi.org/10.1097/hjh.0000000000001039.CrossRefPubMed

22.

Greenbaum LA, Fila M, Ardissino G, Al-Akash SI, Evans J, Henning P, et al. Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int. 2016;89(3):701–11. https://doi.org/10.1016/j.kint.2015.11.026.CrossRefPubMed

23.

Legendre CM, Licht C, Muus P, Greenbaum LA, Babu S, Bedrosian C, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013;368(23):2169–81. https://doi.org/10.1056/NEJMoa1208981.CrossRefPubMed

24.

Vaisbich MH, de Andrade LGM, de Menezes Neves PDM, Palma LMP, de Castro MCR, Silva CAB, et al. Baseline characteristics and evolution of Brazilian patients with atypical hemolytic uremic syndrome: first report of the Brazilian aHUS Registry. Clin Kidney J. 2022;15(8):1601–11. https://doi.org/10.1093/ckj/sfac097.CrossRefPubMedPubMedCentral

25.

Killick J, Morisse G, Sieger D, Astier AL. Complement as a regulator of adaptive immunity. Semin Immunopathol. 2018;40(1):37–48. https://doi.org/10.1007/s00281-017-0644-y.CrossRefPubMed

26.

Peters K. Physiology and pathology of the C3 amplification cycle: a retrospective. Immunol Rev. 2023;313(1):217–24. https://doi.org/10.1111/imr.13165.CrossRefPubMed

27.

Brocklebank V, Johnson S, Sheerin TP, Marks SD, Gilbert RD, Tyerman K, et al. Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland. Kidney Int. 2017;92(5):1261–71. https://doi.org/10.1016/j.kint.2017.04.028.CrossRefPubMedPubMedCentral

28.

Józsi M, Licht C, Strobel S, Zipfel SLH, Richter H, Heinen S, et al. Factor H autoantibodies in atypical hemolytic uremic syndrome correlate with CFHR1/CFHR3 deficiency. Blood. 2008;111(3):1512–4. https://doi.org/10.1182/blood-2007-09-109876.CrossRefPubMed

29.

Matrat L, Bacchetta J, Ranchin B, Tanné C, Sellier-Leclerc AL. Pediatric atypical hemolytic-uremic syndrome due to auto-antibodies against factor H: is there an interest to combine eculizumab and mycophenolate mofetil? Pediatr Nephrol. 2021;36(6):1647–50. https://doi.org/10.1007/s00467-021-05025-8.CrossRefPubMed

30.

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(1):15–39. https://doi.org/10.1007/s00467-015-3076-8.CrossRefPubMed

31.

Lee JM, Park YS, Lee JH, Park SJ, Shin JI, Park Y-H, et al. Atypical hemolytic uremic syndrome: korean pediatric series. Pediatr Int. 2015;57(3):431–8. https://doi.org/10.1111/ped.12549.CrossRefPubMed

32.

Mele C, Remuzzi G, Noris M. Hemolytic uremic syndrome. Semin Immunopathol. 2014;36(4):399–420. https://doi.org/10.1007/s00281-014-0416-x.CrossRefPubMed

33.

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(1):50–9. https://doi.org/10.2215/cjn.06440616.CrossRefPubMed

34.

Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. Orphanet J Rare Dis. 2011;6(1):60. https://doi.org/10.1186/1750-1172-6-60.CrossRefPubMedPubMedCentral

35.

Loirat C, Frémeaux-Bacchi V. Atypical hemolytic uremic syndrome. In: Geary FG, Schaefer F, editors. Pediatric kidney disease. 2nd edn. Berlin: Springer; 2016. p. 597–632.CrossRef

36.

Sellier-Leclerc AL, Frémeaux-Bacchi V, Dragon-Durey MA, Macher MA, Niaudet P, Guest G, et al. Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol JASN. 2007;18(8):2392–400. https://doi.org/10.1681/asn.2006080811.CrossRefPubMed

Title: Adolescence-onset atypical hemolytic uremic syndrome: is it different from infant-onset?
Authors: Kubra Celegen
Bora Gulhan
Kibriya Fidan
Selcuk Yuksel
Neslihan Yilmaz
Aysun Caltik Yılmaz
Beltinge Demircioğlu Kılıç
Ibrahim Gokce
Aslı Kavaz Tufan
Mukaddes Kalyoncu
Hulya Nalcacıoglu
Sare Gulfem Ozlu
Eda Didem Kurt Sukur
Nur Canpolat
Aysun K. Bayazit
Elif Çomak
Yılmaz Tabel
Sebahat Tulpar
Mehtap Celakil
Kenan Bek
Cengiz Zeybek
Ali Duzova
Zeynep Birsin Özçakar
Rezan Topaloglu
Oguz Soylemezoglu
Fatih Ozaltin
Publication date: 05-05-2024
Publisher: Springer Nature Singapore
Keywords: Hemolytic Uremic Syndrome
Thrombotic Microangiopathy
Eculizumab
Published in: Clinical and Experimental Nephrology / Issue 10/2024
Print ISSN: 1342-1751
Electronic ISSN: 1437-7799
DOI: https://doi.org/10.1007/s10157-024-02505-7

Correction to: Adolescence‑onset atypical hemolytic uremic syndrome: is it different from infant‑onset?

Hemolytic Uremic Syndrome
Correction

Impact of COVID-19 pandemic on care of maintenance hemodialysis patients: a multicenter study

Open Access
COVID-19
Original article

Protocol for the nationwide registry of patients with polycystic kidney disease: japanese national registry of PKD (JRP)

Polycystic Kidney Disease
Original article

Neferine alleviates acute kidney injury by regulating the PPAR-α/NF-κB pathway

Acute Kidney Injury
Original article

Protective effects of pioglitazone in renal ischemia–reperfusion injury (RIRI): focus on oxidative stress and inflammation

Pioglitazone
Review article

High body mass index and triglyceride levels at health checkups increase the risk of new-onset chronic kidney disease and worsening renal function: the TAMA MED Project-CKD

Open Access
Chronic Kidney Disease
Original article

Keynote series | Spotlight on menopause

Menopause
Video Series

Menopause can have a significant impact on the body, with effects ranging beyond the endocrine and reproductive systems. Learn about the systemic effects of menopause, so you can help patients in your clinics through the transition.

Prof. Martha Hickey

Dr. Claudia Barth

Dr. Samar El Khoudary

Developed by: Springer Medicine

Watch now

Keynote webinar | Spotlight on adolescent vaping

Pediatrics
On-demand webinar

Growing numbers of young people are using e-cigarettes, despite warnings of respiratory effects and addiction. How can doctors tackle the epidemic, and what health effects should you prepare to manage in your clinics?

Prof. Ann McNeill

Dr. Debbie Robson

Benji Horwell

Developed by: Springer Medicine

Watch now

Keynote webinar | Spotlight on modern management of frailty

Frailty in Geriatric Patients
On-demand webinar

Frailty has a significant impact on health and wellbeing, especially in older adults. Our experts explain the factors that contribute to the development of frailty and how you can manage the condition and reduce the risk of disability, dependency, and mortality in your patients.

Prof. Alfonso Cruz-Jentoft

Prof. Barbara C. van Munster

Prof. Mirko Petrovic

Developed by: Springer Medicine

Watch now

A quick guide to ECGs

Electrocardiography
Training Course

Improve your ECG interpretation skills with this comprehensive, rapid, interactive course. Expert advice provides detailed feedback as you work through 50 ECGs covering the most common cardiac presentations to ensure your practice stays up to date.

PD Dr. Carsten W. Israel

Developed by: Springer Medizin

Start the cases

At a glance: The STEP trials

Obesity
Clinical Trial Summary

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote series | Spotlight on menopause

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content