Extra-Renal manifestations of atypical hemolytic uremic syndrome in children
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Atypical hemolytic uremic syndrome (aHUS) is a chronic disease characterized by thrombotic microangiopathy and a high risk of end-stage kidney disease. Dysregulation and/or excessive activation of the complement system results in thrombotic microangiopathy. Interest in extrarenal manifestations of aHUS is increasing. This study aimed to determine the clinical characteristics of patients with extrarenal manifestations of aHUS in childhood.
This study included 70 children with extrarenal manifestations of HUS from the national Turkish aHUS Registry. The demographics, clinical characteristics, genetic test results, all treatments, and renal/hematologic status of aHUS patients with extrarenal involvement were recorded.
The most common extrarenal manifestation was neurological system involvement (n = 46 [27.2%]), followed by gastrointestinal (n = 20 [11.8%]), cardiovascular (n = 12 [7%]), and respiratory (n = 12 [7%]) involvement. The patients with neurological involvement had a higher mortality rate and a lower estimated glomerular filtration rate (eGFR) than the other patients at last follow-up. Eculizumab (with or without plasma exchange/plasma infusion) treatment increased the renal and hematologic recovery rates.
The most common and serious extrarenal manifestation of aHUS is neurological involvement and treatment outcome findings presented herein are important to all relevant clinicians.
KeywordsAtypical hemolytic uremic syndrome Children Neurological involvement Extrarenal involvement Eculizumab
Atypical hemolytic uremic syndrome
Central nervous system
Posterior reversible encephalopathy syndrome
This study was supported by the Hacettepe University Scientific Research and Development Office (grant no. 010A101009).
Kibriya Fidan, Nilufer Goknar, and Oguz Soylemezoglu participated in conception, design, analysis and interpretation of data, drafting the article, and revising. Kaan Gülleroğlu, Esra Baskın, Engin Melek, Zeynep Y. Yıldırım, Bora Gülhan, and Zeynep Birsin Özçakar participated in data collection. Fatih Özaltın participated in study design and evaluation of genetic results. All authors contributed to manuscript development and approved the final manuscript.
Compliance with ethical standards
The study protocol was approved by the Hacettepe University Ethics Committee (FON10/03-22) and written informed consent was obtained from the parents of each patient.
Conflict of interest
The authors declare that they have no conflict of interest.
- 4.Noris M, Caprioli J, Bresin E, Mossali C, Pianetti G, Gamba S, Daina E, Fenili C, Castelletti F, Sorosina A, Piras R, Donadelli R, Maranta R, van der Meer I, Conway EM, Zipfel PF, Goodship TH, Remuzzi G (2010) Relative role of complement abnormalities in sporadic and familial aHUS and their impact on clinical phenotype. Clin J Am Soc Nephrol 5(10):1844–1859CrossRefPubMedPubMedCentralGoogle Scholar
- 5.Lemaire M, Femeaux Bacchi V, Schaefer F, Choi M, Tang WH, Le Quintrec M, Fakhouri F, Taque S, Nobili F, Martinez F, Ji W, Overton JD, Mane SM, Nürnberg G, Altmüller J, Thiele H, Morin D, Deschenes G, Baudouin V, Llanas B, Collard L, Majid MA, Simkova E, Nürnberg P, Rioux-Leclerc N, Moeckel GW, Gubler MC, Hwa J, Loirat C, Lifton RP (2013) Recessive mutations in DGKE cause atypical hemolytic-uremic syndrome. Nat Genet 45(5):531–536CrossRefPubMedPubMedCentralGoogle Scholar
- 6.Ozaltin F, Li B, Rauhauser A, An SW, Soylemezoglu O, Gonul II, Taskiran EZ, Ibsirlioglu T, Korkmaz E, Bilginer Y, Duzova A, Ozen S, Topaloglu R, Besbas N, Ashraf S, Du Y, Liang C, Chen P, Lu D, Vadnagara K, Arbuckle S, Lewis D, Wakeland B, Quigg RJ, Ransom RF, Wakeland EK, Topham MK, Bazan NG, Mohan C, Hildebrandt F, Bakkaloglu A, Huang CL, Attanasio M (2013) DGKE variants cause a glomerular microangiopathy that mimics membranoproliferative GN. J Am Soc Nephrol 24(3):377–384CrossRefPubMedGoogle Scholar
- 9.Johnson S, Stojanovic J, Ariceta G, Bitzan M, Besbas N, Frieling M, Karpman D, Landau D, Langman C, Licht C, Pecoraro C, Riedl M, Siomou E, van de Kar N, Walle JV, Loirat C, Taylor CM (2014) An audit analysis of a guideline for the investigation and initial therapy of diarrhea negative (atypical) hemolytic uremic syndrome. Pediatr Nephrol 29:1967–1978CrossRefPubMedGoogle Scholar
- 10.Fremeaux-Bacchi V, Fakhouri F, Garnier A, Bienaimé F, Dragon-Durey MA, Ngo S, Moulin B, Servais A, Provot F, Rostaing L, Burtey S, Niaudet P, Deschênes G, Lebranchu Y, Zuber J, Loirat C (2013) Genetics and outcome of atypical hemolytic uremic syndrome: a nationwide French series comparing children and adults. Clin J Am Soc Nephrol 8:554–562CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Caprioli J, Castelletti F, Bucchioni S, Bettinaglio P, Bresin E, Pianetti G, Gamba S, Brioschi S, Daina E, Remuzzi G, Noris M, International Registry of Recurrent and Familial HUS/TTP (2003) Complement factor H mutations and gene polymorphisms in haemolytic uraemic syndrome: the C-257T, the A2089G and the G2881T polymorphisms are strongly associated with the disease. Hum Mol Genet 12:3385–3395CrossRefPubMedGoogle Scholar
- 14.Seddon MJ, Yu Y, Miller EC, Reynolds R, Tan PL, Gowrisankar S, Goldstein JI, Triebwasser M, Anderson HE, Zerbib J, Kavanagh D, Souied E, Katsanis N, Daly MJ, Atkinson JP, Raychaudhuri S (2013) Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration. Nat Genet 451:366–370Google Scholar
- 17.Greenbaum LA, Fila M, Ardissino G, Al-Akash S, Evans J, Henning P, Lieberman KV, Maringhini S, Pape L, Rees L, van de Kar N, Vande Walle J, Massayo O, Bedrosian CL, Licht C (2016) Eculizumab is a safe and effective treatment in pediatric patients with atypical hemolytic uremic syndrome. Kidney Int 89(3):701–711CrossRefPubMedGoogle Scholar
- 24.Loirat C, Fakhouri F, Ariceta G, Besbas N, Bitzan M, Bjerre A, Coppo R, Emma F, Johnson S, Karpman D, Landau D, Langman CB, Lapeyraque AL, Licht C, Nester C, Pecoraro C, Riedl M, van de Kar NC, Van de Walle J, Vivarelli M, Frémeaux-Bacchi V, HUS International (2016) An international consensus approach to the management of atypical haemolytic uremic syndrome in children. Pediatr Nephrol 31:15–39CrossRefPubMedGoogle Scholar
- 25.Geerdink LM, Westra D, Wijk V, Dorresteijn EM, Lilien MR, Davin JC, Kömhoff M, Van Hoeck K, van der Vlugt A, van den Heuvel LP, van de Kar NC (2012) Atypical hemolytic uremic syndrome in children: complement mutations and clinical characteristics. Pediatr Nephrol 27:1283–1291CrossRefPubMedPubMedCentralGoogle Scholar