Although it is becoming less of an issue for many these days because the advent of eculizumab/ Ravulizumab saves them from it, but how to support transplants for dialysis patients with susceptibility to aHUS remains important to some patients.
Probably more than there should be because of the inaccessibility to the complement inhibitor, and an untimely aHUS diagnosis still results in aHUS patients suffering end stage kidney failure.
aHUS transplants present challenges to an already challenging situation.
Back in the days when eculizumab was not available, nor had its use been trialed in Alexion trials for aHUS , one research study stood out on how to use eculizumab for an aHUS kidney transplant. It was led by Professor Julien Zuber of the Necker Hospital, Paris and was a collaboration of the French Study Group for aHUS.
Prof. Julien Zuber
The study’s results were published in 2012. Its conclusions were based on the evidence from 22 transplant cases where eculizumab had been available “off label”, including compassionately. The full article can be seen by clicking on the title below.
Nine of the recipients were given eculizumab prophylactically and the others only on aHUS recurrence.
Apart from one patient, who lost the kidney graft quite quickly because of a clot in the donated kidney , the other eight suffered no recurrence of aHUS. The thirteen who had aHUS recurrence and who received eculizumab as a rescue therapy recovered but their level of kidney graft harm resulted in poorer residual kidney function depending on the extent of the delay to rescue.
The French Group provided a transplant strategy for aHUS kidney transplant decisions in France which became the basis for many future aHUS patients transplants around the world. The strategy was all but replicated in the guidance resulting from the KDIGO conference in 2016.
One of the highlights of the Complement Conference held in Toronto on 6/7 March 2020 was a talk by Julien which brought the French Study group’s conclusions on eculizumab supported kidney transplants up to date.
His talk , with illustrations and findings from a paper published in the last days of December 2019 , confirmed that the 2012 strategy of prophylactic eculizumab use was indeed better but recommended that treatment be more personalised based on genetic susceptibility risk differences. An abstract of the article can be seen by clicking on the title below ( some of tables and charts of the full article are also visible)
The conclusions of this aHUS French Study Groups Research , again led by Julien are based on what happened to aHUS patients enrolled in the French National aHUS Registry. There were two studies
The first was of 119 patients who had had 126 transplant between them from January 2007 and whose genetic susceptibility was known.
The other was about what had happened to 397 adult patients with aHUS enrolled in the Registry from January 2007 until 2016.
The first study showed that prophylaxis eculizumab led to better outcomes for transplanted patients both in quality of kidney graft function and survival but it depended on recurrence risk stratification based on genetic susceptibility.
The second showed that in the post eculizumab era i.e. since 2012 ,the proportion of aHUS transplant survivors among those who had end stage renal failure had increased from 42.6% to 72.3% .
Prophylaxis strategy has had a significant impact but as the French Group conclude perhaps there should be randomised trials. Whilst that would satisfactorily answer the patients’ research question
3.5 Is there a significant difference in outcome between having a complement inhibitor before or after a kidney transplant?
once and for all, patient safety would need to be paramount as is the case for withdrawal of eculizumab studies.
The French aHUS Study Group continue to lead on transplants and aHUS and transplant patients in France and elsewhere have benefitted.
Julien presented the some other findings for the adult cohort in the French Registry over the period 2007 to 2016.
In 2007 there were 173 enrolled. Since then 43 children have become adults , and 33 adults have been lost to follow up and another 39 patients have died. But another 175 adults have onset and enrolled. By 2016 there were 325 adult patients surviving.
An almost doubling of the French enrolled patient prevalence. Quite remarkable.
What an aHUS awareness opportunity to let people know that
Along with the Andrew Siedlecki Group research featured on the Global Action website last year ( click HERE) there is now sufficient evidence for potential aHUS transplant patients to advocate for themselves before a transplant decision.
.For doing less harm to you eculizumab before surgery is better if your genetic susceptibility is high or moderate risk.
Hopefully there will be a video record of Julien’s talk at the Toronto Complement Conference to share eventually.
Finally recollecting his first experience of an eculizumab transplant Julien told the conference about a young girl in France who had onset with aHUS at 6 years old because of a CFH genetic susceptibility. She spent most of her childhood on kidney dialysis until at 23 she received a transplant with compassionate eculizumab provision. It worked and still does ten years on. She even had a baby with both a transplant and eculizumab. It made a difference.
aHUS Global Action got the opportunity to ask Julien a question about de novo aHUS in living donors who are susceptible to aHUS as there has been strong advice against such donations. Juliens reply was ”The question was about whether I would reconsider the living donation from a relative for a recipient with neither complement gene mutation nor homozygous CFH-H3 haplotype. And the answer is definitively YES. Now we have firmly established that the lack of mutation / CFH-H3 haplotype was associated with a very limited risk of post-transplant recurrence, we can infer that the same is true for the donor. “
Another answer which makes genetic susceptibility testing of family members more important.