A Patients and Families Support Group

A UK website about atypical Haemolytic Uraemic Syndrome (aHUS)

Medical Matters

Professor Tim Goodship answers some questions about aHUS. Although he cannot give a personal consultation, aHUSUK members are invited to ask questons about aHUS- its causes, its treatment, its future. Please use the comments page below and someone from aHUSUK will pass on your question.


aHUSUK    Once “something” triggers an episode of HUS how soon after on- set will there be evidence of anaemia and uraemia for a doctor to identify that something is happening which could be HUS and which should be acted upon? What should a doctor be looking for?

Professor Tim Goodship (PTG)    Within a few days there might be evidence of aHUS developing. Evidence of this that a doctor might look for includes the presence of blood and protein in the urine, a rise in the blood creatinine, a fall in haemoglobin, a fall in the platelet count and  a rise in a substance called LDH”

*****


aHUSUK    It is understood that there is a difference between typical and atypical forms of HUS with the former being related to E.coli 0157 poisoning. If someone has an aHUS genetic mutation and is also unfortunate to get E. coli poisoning will it mean that an a HUS episode will definitely be triggered in them?

PTG    There certainly have been reports of individuals within families with a known aHUS gene mutation in whom the disease has been triggered by exposure to E.coli O157.  We don’t, however, know whether an episode would, however, definitely be triggered.

*****

aHUSUK   Is there such a disease as aHUS/TTP as it is has been said that each is caused by different genetic defects and would be treated differently?

PTG    HUS and TTP are names that have been given historically in medical journals when a physician has seen a patient or group of patients who have presented in a similar way. TTP was first used in 1947 and HUS in 1955.  TTP is now usually used to describe a condition where there are either acquired (autoantibodies) or inherited (genetic) abnormalities of a substance called ADAMTS13. This substance has an important role in “dissolving” blood clots which might form in blood vessels. aHUS is now used to describe a condition where there  are often either acquired or inherited abnormalities of complement.  There is, however, overlap between the two conditions which might lead to somebody been given a diagnosis of aHUS/TTP.

*****

aHUSUK   It is possible that some people with a known aHUS related mutation might never have an episode of aHUS like others in their family who do. Why is this and what have “polymorphisms” got to do with it?

 PTG   It is true that not everybody with a known aHUS mutation will develop the disease. We think that this is because a trigger (such as pregnancy) and additional genetic susceptibility (polymorphisms) are needed.

*****

aHUSUK    Some children, known to have an aHUS genetic mutation, after an episode of aHUS may go into remission. When such  children becomes ill and may show some symptoms which could be aHUS related, but which do not “develop”, could something minor still be happening in the complement process and which could be causing long term problems?

PTG   I don’t think we know the answer to this.  It is possible that individuals could have minor episodes of aHUS which resolve. If this does happen then theoretically it could cause long-term problems but I think we need to undertake research in this area.

*****

aHUSUK   Some aHUS patents end up on dialysis, does this mean aHUS can no longer affect them, or are they just in remission and could still have episodes, including sub-clinical events?

PTG   In most individuals with aHUS the disease looks to become quiescent once the kidneys have become irrecoverably damaged. In a few individuals on dialysis you can sometimes see evidence of the disease affecting other organs but this is rare.

***** 

 aHUSUK Patients with an aHUS genetic mutation may be treated by peritoneal dialysis. It s understood that peritoneal dialysis triggers a complement cascade each time it is performed .Could this be a problem for aHUS patients and could this have an effect on their peritoneum and cause long term problems?

 PTG I don’t think we have sufficient information to be able to answer this.  Theoretically it is possible but again this is an area where we need to do some research.

*****

aHUSUK    Living donors who have an aHUS genetic mutation are not recommended to donate a kidney because they could have an aHUS episode post donation even though they have not an episode before. Is there significant statistical evidence to support such a policy and with the benefit of new therapies could there now be some relaxation?

 PTG   There have been at least four living related donors who have gone on to develop aHUS within a year of donation.  I think that this is more than a coincidence but don’t have firm statistical evidence to prove this.  I think that even with new therapies that it is very unlikely that a known unaffected mutation carrier would be accepted as a potential donor.

*****

aHUSUK    Now that eculizumab exists and that one of the complexities of managing a successful transplant is removed do you recommend that all aHUS patients in the UK on dialysis should now be asking their renal units to be referred for a transplant listing, if they have not already been listed?

 PTG   Yes I do.

***** 

aHUSUK    Eculizumab needs to be infused every two weeks or so .If a national service is approved does this mean that all aHUS patients will always have to visit their hospital for this to be done?

PTG    No if the national service is approved there is provision within this for the eculizumab to be administered at home.

*****

aHUSUK    Recently Kidney Research UK announced that they have funded a registry of rare renal disease patients to help with future research. Should aHUS patients expect to be included in that register and should their hospital be doing something to include them?

  PTG    There are in fact going to be two registries of aHUS! One is being developed by Alexion to primarily monitor the long-term outcomes of patients receiving eculizumab but it will also include patients who are not receiving eculizumab. The other registry is the rare renal disease registry which is funded by Kidney Research UK. This will include not only patients with aHUS but also other rare renal diseases. Both registries are in the process of being set up.