Towards precision medicine in atypical haemolytic uraemic syndrome
New research from Professor David Kavanagh and his team in Newcastle, supported by Kidney Research UK, has shown that genetic information can help predict which patients diagnosed with atypical haemolytic uraemic syndrome (aHUS) will respond to treatment with a medication called eculizumab. This research builds on previous breakthroughs in the management of aHUS by this group and offers hope of a more personalised approach.
The pathway to a new treatment option for aHUS patients
aHUS is a rare kidney condition, which arises when blood vessels within the kidney’s filters become blocked and damaged by blood clots. The mechanisms that lead to aHUS were identified by the Newcastle-based team over many years with support from earlier Kidney Research UK grants.
Professor David Kavanagh commented: “Finding the biological causes of aHUS was a true breakthrough. Not only did it answer longstanding questions on aHUS, but it also allowed us to start using a medication called eculizumab that specifically blocks the disease mechanisms. This is a great example of how laboratory-based discoveries can bring benefit to patients, and our latest work builds on this discovery by allowing us to identify the individuals who are most likely to benefit from this treatment more accurately.”
aHUS is most commonly caused by problems with a part of the immune system called ‘complement’ which is involved in protecting us from bacteria and viruses. Our own cells are normally safeguarded from complement, but in people with aHUS this system is faulty owing to certain genetic changes (‘mutations’) and this can lead to kidney failure.
Following the work at Newcastle University, a treatment called eculizumab has been identified as able to block the pathway to kidney damage in some patients with aHUS. Initial studies have suggested that eculizumab can prevent kidney failure in patients with recent-onset aHUS and may also be given to stop recurrence of aHUS in transplanted kidneys.
New results support more effective use of eculizumab
The latest research, published in Blood, looked at medical and biological information from patients with aHUS, and genetic mutations putting them at risk of kidney damage from complement, referred for treatment to the National Renal Complement Therapeutics Centre (NRCTC) in Newcastle.
Results showed that following treatment with eculizumab only 14% of patients required dialysis, compared with 60% of patients who were diagnosed and treated before eculizumab was available. The researchers found that several factors were linked to how well eculizumab-treated patients responded, including the type of genetic mutation, how healthy their kidneys were when aHUS was diagnosed and their age.
Dr Vicky Brocklebank, a Kidney Research UK clinical training fellow added; "Although eculizumab is a life-changing treatment option for many patients, it is expensive and can have serious side effects. This large-scale study not only confirms that eculizumab can prevent kidney failure in many patients with aHUS, but also helps us to identify those who will benefit most. Further work is ongoing to support those aHUS patients who do not see benefits from eculizumab treatment.”
Building a centre of expertise for aHUS
Owing to the cost of eculizumab, and the specialist clinical and diagnostic evaluation needed to identify and manage aHUS, a NHS England highly specialist centre for aHUS was set up in Newcastle - the NRCTC.
Alongside providing medical support for patients, the NRCTC is also an important centre for research into aHUS and has been supported by several research grants from organisations including Kidney Research UK.
Dr Aisling McMahon, executive director of research and policy at Kidney Research UK added, “This work by David, Vicky and the Newcastle team is a really important example of how, with collaboration between several partners, laboratory research can lead to clinical benefits for patients. We are delighted to have been a significant partner in this research and look forward to future projects supporting patients with aHUS.”
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