Soliris enables successful second kidney transplant: Case study
Woman with aHUS continues medication, remains stable 4 years later
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A woman with atypical hemolytic uremic syndrome (aHUS) successfully underwent a second kidney transplant as treatment with Soliris (eculizumab) largely prevented or eased the complications that led to failure of her first transplant.
The medication has helped stabilize the woman’s kidney function for four years, researchers wrote in a case study, ”Measurement of complement proteins may aid interpretation of pathophysiology in kidney transplant recipients with atypical hemolytic uremic syndrome,” published in CEN Case Reports.
aHUS is caused by abnormal activity of the complement cascade, a part of the immune system. This results in thrombotic microangiopathy (TMA), or the formation of blood clots in small blood vessels that can damage internal organs; hemolytic anemia (when red blood cells are destroyed more quickly than they are produced); low platelet levels; and acute kidney failure.
The 53-year-old woman from Japan had kidney failure, attributed to preeclampsia, a serious pregnancy complication characterized by high blood pressure and signs of kidney damage. She was diagnosed with aHUS after undergoing a kidney transplant from an unrelated donor.
The graft, however, softened within 30 minutes. A biopsy of the transplanted kidney showed signs of TMA, which doctors initially thought was a rejection reaction to the transplanted kidney. Lab tests indicated low platelet levels a day after the surgery, and blood creatinine levels (a measure of kidney function) and urine output deteriorated despite treatment. Graft function and health worsened in subsequent days, and the woman showed evidence of hemolytic anemia. Doctors started hemodialysis, a treatment that temporarily takes over the kidneys’ role by removing waste from the blood using a machine.
No mutations, antibodies
Although the woman had no detectable disease-causing mutations or antibodies, testing revealed overactivation of the complement system.
Based on a full review of the woman’s medical data, she was eventually diagnosed with aHUS. Lab tests showed no signs of post-transplant antibody-mediated rejection, drug-mediated TMA, or mutations in complement-related genes.
A second transplant was then planned, this time with a family member as the donor. In this case, the woman received plasma exchange treatment to remove possible abnormal complement-related proteins. She also received Soliris before the transplant, together with immunosuppressants used in the first surgery.
The woman showed no signs of TMA immediately after the second transplant, but she showed elevated blood creatinine levels and weak TMA in a kidney biopsy nine days after the surgery. Kidney function gradually improved following immunosuppressant treatment. She was given an additional dose of Soliris after an increase in complement activity.
Soliris was discontinued one month post-transplant, after a kidney biopsy revealed normal tissue. A subsequent increase in creatinine levels and signs of TMA four months after surgery prompted doctors to restart Soliris. The woman has since been stable, and has shown no evidence of TMA and good graft function for four years.
Analysis of the woman’s complement-related proteins over time showed abnormal activation, as well as a response to Soliris, illustrated by normalized complement factor levels and eased signs of TMA.
“Although our data were from a single patient, the clinical outcome with eculizumab [Soliris] aligns with published data,” the investigators wrote. “Overall, our data suggest that observation of complement-related protein levels may aid understanding of the [disease] before, during, and after transplant, as well as provide a method to detect kidney transplant candidates at potential risk of aHUS.”
