title: Eculizumab long-term therapy for pediatric renal transplant in aHUS with CFH/CFHR1 hybrid gene.
abstract: BACKGROUND
  Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) caused by dysregulation of the complement system. Outcomes of kidney transplantation are poor owing to aHUS recurrence and loss of graft. Patients carrying CFH mutations or CFH/CFHR1 hybrid genes present a very high risk of recurrence despite preventive plasmapheresis. Evaluation of recent data suggests that prophylactic eculizumab pretransplant might be the preferred therapy if available.
  
  
  METHODS
  We report 3-year follow-up data in a 9-year-old boy with aHUS and successful renal transplant treated with prophylactic eculizumab without recurrence. He presented with aHUS at age 3, irreversible renal failure and uncontrolled severe hypertension with concentric left ventricular hypertrophy, recurrent acute pulmonary edema, and congestive heart failure despite five hypotensive agents and bilateral nephrectomy. Complement analysis demonstrated the presence of a CFH/CFHR1 hybrid gene inherited from his mother and a SNP risk CFH haplotype inherited from his father. Kidney transplant was performed with prophylactic eculizumab and subsequent fortnightly administration. Three years post-transplant, graft function remains stable (serum creatinine 0.9 mg/dl), hypertension is controlled, no left ventricular hypertrophy, no opportunistic infections, and negative clinical chemistry parameters for hemolysis.
  
  
  CONCLUSIONS
  Eculizumab is a safe and effective therapy for preventing TMA recurrence and provides long-term graft function in aHUS with the CFH/CFHR1 hybrid gene.
authors: Pediatric Nephrology Unit, Hospital La Fe, Bulevar sur s/n, 46026, Valencia, Spain, eroman@comv.es.
authors: Elena
authors: E
authors: Román-Ortiz
authors: Santiago
authors: S
authors: Mendizabal Oteiza
authors: Sheila
authors: S
authors: Pinto
authors: Margarita
authors: M
authors: López-Trascasa
authors: Pilar
authors: P
authors: Sánchez-Corral
authors: Santiago
authors: S
authors: Rodríguez de Cordoba
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome; D002648:Child; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics / Q000628:therapy*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D050506:Mutant Chimeric Proteins / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C517622:CFH-CFHL1 protein, human; D050506:Mutant Chimeric Proteins; C481642:eculizumab
references: Immunobiology. 2012 Nov;217(11):1034-46
references: 22964229
references: Mol Immunol. 2004 May;41(1):81-4
references: 15140578
references: Clin J Am Soc Nephrol. 2011 Jun;6(6):1488-94
references: 21617085
references: PLoS Med. 2006 Oct;3(10):e431
references: 17076561
references: Nat Rev Nephrol. 2012 Nov;8(11):643-57
references: 23026949
references: Am J Transplant. 2012 Dec;12(12):3337-54
references: 22958221
references: Am J Transplant. 2009 Nov;9(11):2644-5
references: 19775316
references: N Engl J Med. 2009 Jan 29;360(5):544-6
references: 19179329
references: Nat Rev Nephrol. 2011 Jan;7(1):23-35
references: 21102542
references: Am J Transplant. 2012 Jul;12(7):1938-44
references: 22494769
references: Kidney Int. 2012 Jan;81(1):56-63
references: 21881555
references: J Am Soc Nephrol. 2008 Mar;19(3):639-46
references: 18235085
references: Hum Mol Genet. 2005 Mar 1;14(5):703-12
references: 15661753