Eculizumab long-term therapy for pediatric renal transplant in aHUS with CFH/CFHR1 hybrid gene

Pediatr Nephrol. 2014 Jan;29(1):149-53. doi: 10.1007/s00467-013-2591-8. Epub 2013 Aug 24.

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.

Case-diagnosis/treatment: 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.

Conclusion: 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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Atypical Hemolytic Uremic Syndrome
  • Child
  • Hemolytic-Uremic Syndrome / genetics
  • Hemolytic-Uremic Syndrome / therapy*
  • Humans
  • Kidney Transplantation*
  • Male
  • Mutant Chimeric Proteins / genetics*

Substances

  • Antibodies, Monoclonal, Humanized
  • CFH-CFHL1 protein, human
  • Mutant Chimeric Proteins
  • eculizumab