Fund raising, which began when aHUSUK still existed, has been put to use to help fund research which may improve the aHUS diagnosis process.
Readers of this website may have seen, in the series of articles about aHUS patients experience of aHUS diagnosis, the difficulty of deciding the causes of thrombotic microangiopathies. Biopsies may detect TMA but whether any uncontrolled complement is even involved, let alone whether it is down to aHUS, is elusive. But knowing would speed up effective treatment.
Some answers to that may be in the kidney biopsies of patients who have been diagnosed with aHUS or not.
A research project by the renal complement expert centre in Newcastle Hospitals and Oxford University Hospitals has recently been funded by Kidney Research UK to study how such specific identification may be possible.
Here is the announcement by KRUK.
Using the kidney biopsy to personalise management of atypical haemolytic uraemic syndrome
With combined funding from Kidney Research UK general funds and the aHUS restricted fund, Professor David Kavanagh from Newcastle University and Professor Ian Roberts from Oxford University Hospitals will study ways to identify which kidney patients will respond to drug treatment for atypical haemolytic uremic syndrome (aHUS).
What is aHUS?
aHUS is a destructive kidney condition that affects a patient’s immune system, causing it to attack their kidney cells. Until recently, most patients with aHUS developed kidney failure. Kidney transplant was not previously possible as the disease would attack and destroy the new kidney just as it did the patient’s own kidney. This meant that patients often required long-term dialysis treatment.
Our research led to a breakthrough drug treatment, but not all patients respond
In the late 1990s, pioneering research led by Professor Tim Goodship at Newcastle University, funded by Kidney Research, revealed how aHUS causes damage to the kidneys and ultimately led to the successful introduction of the drug eculizumab into clinical practice via the National Renal Complement Therapeutics Centre in Newcastle
Eculizumab works by stopping part of the immune system which is overactive in patients with aHUS. Although it is usually successful in treating patients with aHUS, there is a small group of patients who do not respond to the drug, but there is no way of quickly identifying these patients before treatment. As eculizumab suppresses the immune system, its use carries an increased risk of infections that can lead to meningitis, so it is vital that patients who don’t stand to benefit are not given the drug.
Finding a solution
We have awarded Professor David Kavanagh from Newcastle University and Professor Ian Roberts from Oxford University Hospitals with a research project grant to look at the kidney biopsies of aHUS patients to see if it is possible to identify characteristics that would predict who will respond to eculizumab and recover kidney function.
When a kidney biopsy of an aHUS patient is examined under the microscope it reveals damage to the lining of the blood vessels which is called thrombotic microangiopathy (TMA).
Until recently Atypical Haemolytic Uraemic Syndrome was a disease where most patients developed kidney failure requiring long term dialysis. Additionally, for those patients who developed kidney failure the high relapse rate following renal transplantation meant a lifetime on dialysis. In the late 1990s research in Newcastle elucidated the role of complement in the pathogenesis of aHUS. This ultimately led to the successful introduction of the complement inhibitor eculizumab into clinical practice via the NRCTC in Newcastle. Although usually successful in patients, eculizumab is a drug that suppresses the immune system and leads to a high incidence of meningococcal infection- frequently causing meningitis (an increased rate of ~600 times).
Work at the NRCTC has recently identified a subgroup of patients who do not respond to eculizumab however we do not have a rapid test to identify these patients. The aim of this study is to look at the kidney biopsies of aHUS patients to see if it is possible to identify characteristics that would predict who will respond to eculizumab and recover kidney function. This will prevent patients who will not benefit from eculizumab being put at risk of meningitis.
This important project has been part funded by a restricted fund that was transferred to us some time ago for the benefit of aHUS research(£79k) and complements our funding of £121k to jointly make this award possible. The total cost of the project is £200,000 over two years, comprising £155,414 salary costs and £44,586 materials and consumables.
What could this mean for kidney patients?
This is another step towards the personalisation of treatment and medicines for patients and families at risk of aHUS. This work will ultimately prevent patients who will not benefit from eculizumab being put at risk of meningitis.
Article No. 540