Eculizumab induces long-term remission in recurrent post-transplant HUS associated with C3 gene mutation.
A 15-year-old male patient developed atypical hemolytic uremic syndrome (aHUS) at 16 months of age leading to end-stage renal disease. The family history was suggestive of autosomal dominant aHUS, and he was more recently found to have a C3 heterozygous gene mutation (1835C>T mutation in exon 14, which determines the amino-acidic substitution R570W) with no other complement abnormalities. He had two renal transplants, the first at 2.5 years, and the second at 8 years of age, but allograft dysfunction developed in both transplants leading to graft failure due to recurrent HUS at 5 years and 18 months post-transplantation respectively. At 15 years of age he received a third transplant from a deceased donor with pre-emptive plasmapheresis. He had immediate graft function and nadir serum creatinine was 1.3-1.4 mg/dl. Severe allograft dysfunction and hypertension developed 2 months after transplantation following influenza infection. Renal allograft biopsy showed thrombotic microangiopathy. He received plasmapheresis followed by eculizumab therapy. Allograft function returned to baseline 3 weeks after starting therapy, and post-treatment allograft biopsies showed improvement in thrombotic microangiopathy. He continues to receive eculizumab every 2 weeks with stable graft function 13 months after transplantation.
Division of Pediatric Nephrology, Driscoll Children's Hospital, Corpus Christi, TX 78411, USA. Salakash@hotmail.com
Samhar I
SI
Al-Akash
P Stephen
PS
Almond
Van H
VH
Savell
Salam I
SI
Gharaybeh
Cris
C
Hogue
D000293:Adolescent; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D003176:Complement C3 / Q000235:genetics*; D006085:Graft Survival / Q000187:drug effects*; D006463:Hemolytic-Uremic Syndrome / Q000150:complications / Q000188:drug therapy* / Q000601:surgery; D006801:Humans; D007676:Kidney Failure, Chronic / Q000601:surgery*; D016030:Kidney Transplantation; D008297:Male; D009154:Mutation; D012008:Recurrence; D012074:Remission Induction
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D003176:Complement C3; C481642:eculizumab