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Eculizumab use before kidney transplant may reduce risk of future dialysis, improve outcomes
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Patients who are diagnosed with atypical hemolytic uremic syndrome before kidney transplantation and who subsequently receive eculizumab either before or during the transplant may both have better outcomes and a lessened need for dialysis post-transplant than those who begin eculizumab therapy after transplant, according to a recently published study.
“Our findings from this observational study suggest eculizumab is beneficial for the treatment of patients with [atypical hemolytic uremic syndrome] aHUS in the setting of transplantation, and carries a minimal risk of infection,” Andrew M. Siedlecki, MD, of Brigham and Women’s Hospital in Boston, and colleagues wrote. “More specifically, they support the hypothesis that initiation of eculizumab therapy before transplantation potentially reduces rates of dialysis after transplantation with the condition that timing of aHUS diagnosis influences posttransplant outcome. Those patients who were diagnosed with aHUS and receiving treatment with eculizumab at the time of transplantation also enjoyed better 3-year allograft function.”
To investigate whether initiating eculizumab before kidney transplant reduced dialysis incidence post-transplant, researchers used data from the Global Atypical Hemolytic Uremic Syndrome Registry. The study included 188 patients (median age at time of transplant, 34.1 years; 56% were women; 88% were white) who had at least one kidney transplant, were treated with eculizumab and were enrolled between April 2012 and May 2017. Patients were categorized into one of two primary groups: initiating eculizumab before kidney transplant or initiating eculizumab after kidney transplant. Group 1 consisted of 88 patients who all had also been diagnosed with atypical hemolytic uremic syndrome before transplant and group 2 was further divided into two subgroups of diagnosis before (n = 52) or after (n = 48).
Researchers found that, within 5 years of transplantation, 47 patients needed dialysis and that the risk of dialysis after transplantation was higher in the group that both started eculizumab after transplant and did not receive an atypical hemolytic uremic syndrome diagnosis until after transplant than the group that started eculizumab before transplant (HR = 4.6; 95% CI; 1.7-12.4).
In addition, patients who started eculizumab before transplant had better graft function than the other groups within 6 months (median estimated glomerular filtration rate, 60.6 ml/min per 1.73 m2 vs. 31.5 ml/min per 1.73 m2 in the group that received diagnosis pre-transplant but no eculizumab until after vs. 9.6 ml/min per 1.73 m2 in the group that received diagnosis post-transplant; P = .004 and P= .0001, respectively).
Researchers also noted that one meningococcal infection that was resolved with treatment was reported, as were three deaths unrelated to eculizumab.
“Overall, these data align with current guidelines suggesting that the diagnosis of aHUS should be made as early as possible for early initiation of appropriate treatment to obtain optimal patient outcomes, and that such recommendations also apply in the transplant setting,” the researchers wrote. – by Melissa J. Webb
Disclosures: Siedlecki reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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