Soliris Boosts Success of Kidney Transplants in Small aHUS Study

Yedida Y Bogachkov PhD avatar

by Yedida Y Bogachkov PhD |

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Soliris | aHUS News | illustration of kidneys

Soliris (eculizumab) prevented disease recurrence in a small group of patients with primary atypical hemolytic uremic syndrome (aHUS) after they underwent kidney transplantation, a recent study has found.

The study, “Efficacy and Safety of Eculizumab in Kidney Transplant Patients With Primary Atypical Hemolytic-Uremic Syndrome,” was published in the journal Transplantation Proceedings.

aHUS leads to the formation of small blood clots, particularly in the kidneys, due to abnormal activity of the complement cascade, a part of the immune system. People with aHUS often experience disease recurrence after undergoing a kidney transplant, particularly if they have specific alterations in proteins that regulate the complement cascade. This, in turn, can lead to the loss of the newly transplanted organ.

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Research has shown that treating patients with Soliris prior to the procedure leads to a better prognosis and increases the chances of transplant success.

Soliris inhibits the complement pathway by preventing the complement protein C5 from being cleaved into C5a and C5b. C5a is a proinflammatory molecule and C5b, when combined with other proteins, forms the C5b-9 terminal membrane attack complex, promoting blood clotting. By preventing C5 cleavage, Soliris can prevent clotting within blood vessels.

This study followed six patients with aHUS who received a kidney transplant between July 2017 and July 2020. All received Soliris to treat or prevent an aHUS recurrence.

The mean age of the patients was 44 years, and half of them were women.

Four patients had mutations in the gene that codes for complement factor H (CFH), a protein that helps regulate complement activation.

The other two patients had polymorphisms — DNA sequence variations that are relatively common in the population — in the C3 and MCP genes.

Patients with CFH mutations were considered to be at higher risk for an aHUS recurrence, and were started on Soliris as a preventive measure before undergoing the transplant. The protocol involved administering the medication at a dose of 1,200 mg before the transplant, followed by four doses of 900 mg per week, and then 1,200 mg every two weeks.

Meanwhile, the two patients with the low-risk polymorphisms started treatment with Soliris 15 days and six months after the transplant due to an aHUS recurrence, which was confirmed by a kidney biopsy.

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During the follow-up period, which lasted a mean of 57 months (4.75 years), two patients experienced episodes of acute rejection — when a patient’s immune system launches an attack against the transplanted organ, viewing it as foreign and a potential threat.

None of the patients lost transplanted organ function or died. Moreover, no adverse effects related to the treatment were noted.

“Treatment with [Soliris] is safe and efficient in our kidney transplant population with aHUS and genetic modifications in complement-regulating proteins,” the researchers wrote. “No patient experienced recurrence of the aHUS in the short to medium term when [Soliris] was started before the transplant.”

They noted that studies involving a larger number of patients are required to confirm these findings.