Preventive treatment with Soliris helps in kidney transplant in aHUS
Study finds kidneys still function in 97% of patients 1 year later
Preventive treatment with Soliris (eculizumab) before surgery dramatically improved kidney transplant outcomes in people with atypical hemolytic uremic syndrome (aHUS), according to a recent study.
One year after the surgeries, 97% of transplanted kidneys still functioned in Soliris-treated patients. In those who did not receive preventive treatment, that proportion was 64%.
“Our study demonstrates prophylactic [preventive Soliris] treatment significantly improves kidney transplant survival in patients with aHUS … making it a viable and superior strategy for … these patients,” the researchers wrote.
According to the team, preventive Soliris worked better than reactive treatment given after the procedure.
The study, “Assessing the Impact of Prophylactic Eculizumab on Renal Graft Survival in Atypical Hemolytic Uremic Syndrome,” was published in the journal Transplantation.
Guidelines recommend preventive treatment for transplant patients
aHUS is marked by the formation of blood clots in small blood vessels, leading to organ damage and failure, particularly in the kidneys.
The disease is driven by the abnormal activation of the complement cascade — a part of the immune system that normally helps defend the body against invading microbes. While most aHUS patients carry mutations in genes that regulate the complement cascade, disease onset often requires certain trigger events, such as infections, medications, or other conditions.
In severe cases, a transplant can successfully treat kidney failure. However, disease recurrence within the first year after the transplant is common and results in a high transplant failure rate.
Soliris was approved in the U.S. in 2011 for all aHUS patients and works by suppressing the complement cascade. The therapy has markedly improved kidney outcomes in aHUS patients who have and have not undergone a kidney transplant.
Because of the high risk of recurrence soon after the transplant, prophylactic treatment with Soliris, started at the time of the procedure, has been proposed as a method of preventing aHUS recurrence and damage to the newly transplanted kidneys.
Consistently, the Kidney Disease: Improving Global Outcomes (KDIGO) — a set of guidelines from a global nonprofit organization — has recommended prophylactic treatment for kidney transplant recipients considered to be at a medium or high risk of experiencing disease recurrence.
Using data from the National Renal Complement Therapeutics Center database, researchers in the U.K. now compared the outcomes of aHUS patients who underwent kidney transplants, with or without Soliris prophylaxis.
The team identified 118 kidney transplants in 86 recipients diagnosed with aHUS. Among them, 38 kidney transplants were performed in 38 individuals who received preventive treatment with Soliris. Their outcomes were compared with those of a control group of 33 kidney transplants performed in 32 medium and high-risk patients who did not receive prophylactic treatment with Soliris.
Complement-related genetic defects were similar between the groups, with CFH gene mutations being the most common. Transplant recipients classified as being at a high risk of experiencing aHUS relapse predominated in both the Soliris and control groups (68% vs. 58%).
Analyses revealed a significantly higher proportion of transplanted kidneys continued to function with preventive Soliris compared with the control group (81.6% vs. 33.3%). Significantly fewer transplants failed with Soliris treatment than without it (18% vs. 66.7%).
Graft (transplanted kidney) survival also was significantly better with Soliris treatment than without it. A higher proportion of transplanted kidneys maintained their function in Soliris-treated patients at three months (100% vs. 79%), one year (97% vs. 64%), and three years (89% vs. 61%) after the transplant.
We advocate prophylactic [Soliris] treatment before transplantation, rather than reactive treatment posttransplant, as the better option based on currently available data.
Fewer transplants were lost due to thrombotic microangiopathy — the formation of blood clots in small blood vessels that can damage organs — in treated patients than in controls (2.6% vs. 42.4%).
Among Soliris-treated patients, five died with a functioning transplanted kidney, with four deaths occurring at least two years post-transplant. No deaths with a functioning transplant were reported in the control group.
Regarding genetics, patients with disease-causing CFH gene mutations had high rates of early graft loss, with 42% graft survival one year post-transplant and 35% after three years. Graft survival was higher in patients carrying variants of uncertain significance, or genetic mutations with an unknown clinical impact, with 58% graft survival after one year and 50% after three years.
When assessed by the risk of disease relapse, six-month graft survival was 100% for low-risk recipients, 81% for medium-risk, and 53% for high-risk, “supporting the KDIGO-advised stratification.”
“We advocate prophylactic [Soliris] treatment before transplantation, rather than reactive treatment posttransplant, as the better option based on currently available data,” the researchers wrote.