Use of eculizumab and plasma exchange in successful combined liver-kidney transplantation in a case of atypical HUS associated with complement factor H mutation.
BACKGROUND
Atypical hemolytic uremic syndrome (aHUS) evolves into end-stage renal failure in nearly half of affected patients and is associated with defective regulation of the alternative complement pathway. Patients with a complement factor H (CFH) mutation have a 30-100% risk of graft loss due to aHUS recurrence or graft thrombosis. Since CFH is produced predominantly by the liver, combined liver-kidney transplant is a curative treatment option. One major unexpected risk includes liver failure secondary to uncontrolled complement activation. We report a successful combined liver-kidney transplantation with perioperative plasma exchange and use of the humanized anti-C5 monoclonal antibody eculizumab.


METHODS
An 11-month-old female presented with oliguric renal failure after 3 weeks of flu-like symptoms in the absence of diarrhea. Following the identification of Escherichia coli 0157:H7 in her stool, she was discharged home on peritoneal dialysis with a diagnosis of Shiga toxin-associated HUS. Three months later, she developed severe anemia, thrombocytopenia, and neurological involvement. aHUS was diagnosed and confirmed, and genetic testing revealed a mutation in CFH SCR20. Once donor organs became available, she received preoperative plasma exchange followed by eculizumab infusion with intra-operative fresh frozen plasma prior to combined liver-kidney transplant. At 19 months post-transplant, she continues to have excellent allograft and liver function without signs of disease recurrence.


CONCLUSIONS
Perioperative use of eculizumab in conjunction with plasma exchange during simultaneous liver-kidney transplant can be used to inhibit terminal complement activity, thereby optimizing successful transplantation by reducing the risk of graft thrombosis.
Stanford University, Stanford, CA, USA, hatran@stanford.edu.
Ha
H
Tran
Abanti
A
Chaudhuri
Waldo
W
Concepcion
Paul C
PC
Grimm
D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D065766:Atypical Hemolytic Uremic Syndrome; D017242:Complement Factor H / Q000172:deficiency* / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease; D006463:Hemolytic-Uremic Syndrome / Q000175:diagnosis / Q000209:etiology / Q000601:surgery*; D000081208:Hereditary Complement Deficiency Diseases; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007223:Infant; D007674:Kidney Diseases / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D016030:Kidney Transplantation; D016031:Liver Transplantation; D009154:Mutation; D010641:Phenotype; D010951:Plasma Exchange; D013997:Time Factors; D016896:Treatment Outcome; D015432:Glomerulonephritis, Membranoproliferative
D061067:Antibodies, Monoclonal, Humanized; C493495:CFH protein, human; D007166:Immunosuppressive Agents; D017242:Complement Factor H; C481642:eculizumab