Soliris part of strategy for complex kidney transplant in aHUS case
Complement therapy and immune suppression guided transplant care
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Treatment with Soliris (eculizumab), along with several immune-suppressing medications, was part of a treatment strategy that supported a woman with atypical hemolytic uremic syndrome (aHUS) in receiving a kidney donated from her mother — even though testing showed the two were not fully immunologically compatible.
The case was described in the study, “Successful living kidney transplantation in a T-cell flow cytometry crossmatch-positive patient with atypical hemolytic uremic syndrome treated with an anti-C5 antibody: a case report,” published in CEN Case Reports.
aHUS is a rare disease in which abnormal activity of the complement cascade, a part of the immune system, causes blood clots to form in small blood vessels. This can lead to kidney damage and hemolytic anemia, a form of anemia caused by red blood cells breaking apart.
Woman with aHUS seeks kidney transplant
Doctors in Japan reported the case of a 41-year-old woman admitted to their hospital. She had end-stage kidney failure and needed regular dialysis. She also had frequent anemia — low hemoglobin, the protein that helps red blood cells carry oxygen — and often required blood transfusions. Tests also indicated low platelet counts and signs of red blood cell destruction.
Although genetic testing did not find a clear disease-causing mutation, “in consideration of her clinical course, she was diagnosed with aHUS,” the investigators wrote.
The woman wanted a kidney transplant, with her mother as the donor. Kidney transplants in aHUS can be risky because the disease may recur and damage the transplanted kidney.
Further complicating matters, tests suggested the patient and her mother might not be compatible. They had different blood types, and the patient tested positive for antibodies directed against proteins on her mother’s cells known as human leukocyte antigens (HLA). This resulted in a positive crossmatch test, meaning her immune system was primed to attack the donor kidney, which increased the risk of rejection.
To lower the risk of transplant failure, the team used a combination of medications with two main goals: control aHUS by blocking complement activity, and suppress the immune system to reduce the chance of antibody-driven organ rejection.
Doctors begin Soliris before transplant
Two months before the transplant, the patient began treatment with Soliris, an approved aHUS therapy. Her anemia symptoms, including headache and fatigue, improved after starting treatment. The researchers chose Soliris instead of Ultomiris (ravulizumab-cwvz), another approved aHUS treatment that works in a similar way but is given less frequently, because Soliris’ effects on the complement system can be more easily monitored through blood testing. Careful monitoring was considered essential as the team prepared for the transplant.
About a month before surgery, the woman began more than a half-dozen other therapies to suppress her immune system, including medications commonly used to prevent transplant rejection. At the same time, doctors closely monitored complement activity and adjusted Soliris dosing as needed.
The transplant was successfully performed, and she was discharged from the hospital 14 days later without major complications. One month after the transplant, she was switched from Soliris to Ultomiris. At follow-up one year post-transplant, she maintained good kidney function and showed no signs of antibody-mediated rejection.
“The clinical course of the present case suggests the potential effectiveness of a multifaceted treatment strategy, including [Soliris], for patients [who have antibodies against immune markers on donor organs and are] at risk of aHUS recurrence,” the researchers concluded.
Soliris and Ultomiris are both sold by Alexion, AstraZeneca Rare Disease. One author, Masayoshi Okumi, disclosed consultancies and honoraria from Alexion Pharmaceuticals. The remaining authors reported no conflicts of interest.
