Case Report: Combined Liver-Kidney Transplantation to Correct a Mutation in Complement Factor B in an Atypical Hemolytic Uremic Syndrome Patient

Abstract

Pathogenic gain-of-function variants in complement Factor B were identified as causative of atypical Hemolytic Uremic syndrome (aHUS) in 2007. These mutations generate a reduction on the plasma levels of complement C3. A four-month-old boy was diagnosed with hypocomplementemic aHUS in May 2000, and he suffered seven recurrences during the following three years. He developed a severe hypertension which required 6 anti-hypertensive drugs and presented acrocyanosis and several confusional episodes. Plasma infusion or exchange, and immunosuppressive treatments did not improve the clinical evolution, and the patient developed end-stage renal disease at the age of 3 years. Hypertension and vascular symptoms persisted while he was on peritoneal dialysis or hemodialysis, as well as after bilateral nephrectomy. C3 levels remained low, while C4 levels were normal. In 2005, a heterozygous gain-of-function mutation in Factor B (K323E) was found. A combined liver and kidney transplantation (CLKT) was performed in March 2009, since there was not any therapy for complement inhibition in these patients. Kidney and liver functions normalized in the first two weeks, and the C3/C4 ratio immediately after transplantation, indicating that the C3 activation has been corrected. After remaining stable for 4 years, the patient suffered a B-cell non-Hodgkin lymphoma that was cured by chemotherapy and reduction of immunosuppressive drugs. Signs of liver rejection with cholangitis were observed a few months later, and a second liver graft was done 11 years after the CLKT. One year later, the patient maintains normal kidney and liver functions, also C3 and C4 levels are within the normal range. The 12-year follow-up of the patient reveals that, in spite of severe complications, CLKT was an acceptable therapeutic option for this aHUS patient.

Thrombotic microangiopathy after kidney transplantation: Expanding etiologic and pathogenetic spectra

“…Other preventive measures include pretransplant plasma exchange (PE), use of induction therapy and low doses of CNIs. For some complement regulatory gene mutations, use of liver-kidney transplantation has been used successfully[ 69 ]. This procedure is controversial because of potentially severe postoperative complications but the use of PE or a single dose of eculizumab until graft liver function is adequate greatly improved outcomes for the patient.…”

TMA in Kidney Transplantation

“…In this regard, a successful liver–kidney transplant has been reported in a patient with a gain-of-function CFB mutation. 105 This procedure is controversial because of potentially severe postoperative complications 106 but the use of PE or a single dose of eculizumab until graft liver function is adequate greatly improved outcomes for the patient. 92,104 In any case, this type of transplant should only be performed in centers with proven expertise, after a careful risk-benefit analysis.…”