ASN, aHUS and the sisters from Missouri

Kidney Week 2019 is currently in progress. The American Society of Nephrology’s  annual event is being held in Washington DC and is attended by delegates from around the World.

A quick scan through the Kidney Week APP reveals some ,if fewer,  references to aHUS in the conference talks programme and abstract/posters.

As would be expected Alexion is sponsoring some talks about the diagnosis and treatment of aHUS including one by Dr Andrew Siedlecki ,who the alliance collaborated with for the TMA Boston symposium in 2017.

Alexion’s Ravulizumab for aHUS trial is being reported as well as a study  by the Alexion aHUS Global Registry on the risks of TMA following withdrawal of eculizumab. In doing so that shows the opportunities for safe withdrawal too.

The conference programme also had a talk by Dr Romy N Boumeester and posters featuring the researchers from Radbourd Medical Centre Nijmegen  about withdrawal and personalised dose adjustment of eculizumab. Their important research has featured in articles on this website about CUREiHUS and a patient conference in the Netherlands this time last year.

Dr Gianluigi Ardissino with the abstract about penetrance in families which appeared as a website article last week is also there.

An abstract about “Gender differences in presentation and outcomes among patients with aHUS” by Christof Aig of the Medical University  of Vienna offering some new insights that gender may have on patient’s experience of the disease.

Another two topicsfrom the same University involved a talk by Dr Martina Gaggl on Maternal Pregnancy Outcomes in Women with Complement-Mediated TMA: Update of the Vienna TMA Cohort as well as an abstract presentation about “Successful Pregnancies In Kidney Transplant Recipients with Complement-Mediated Thrombotic Microangiopathy”

These Vienna TMA Cohort studies need to be looked at further at some time

There were two other abstracts also about pregnancy associated aHUS. One from Japan which retrospectively looked at the outcomes of six Japanese aHUS Patients onsetting post partum and how they recovered and how one had a trouble free second pregnancy.

The other was from the USA and presented by Doctors from the Washington University, St Louis. It is a case study ( and story ) about the pregnancies of three Hispanic sisters from Missouri.

Each of them experienced post-partum  symptoms within 7,7 and 10 days  of their deliveries in 2006 , 2014  and  2015 at ages of 18, 24 and 25 respectively.

The  first and second sister had identical symptoms of anaemia , thrombocytopenia and acute kidney injury but did not get an aHUS diagnosis, even though the first sister’s  kidney biopsy had revealed evidence of TMA. The third sister also had a kidney biopsy showing evidence of TMA and was diagnosed with aHUS and treated with PEX and dialysis until she experienced acute heart failure and was treated with Eculizumab, and within two weeks she had recovered. The first sister had also experienced acute heart failure and recovered. The second sister was then diagnosed as having aHUS given eculizumab and then after two years stopped dialysis.

Genetic testing was undertaken and each sister had multiple variants/mutations in their Complement factors H , I  and MCP. The multiple genetic variants had  increased the risk of onset. Where did they  come from as there is no mention of the sister’s mother having experienced difficulties in pregnancy?  The researchers do however reveal that their fathers’s mother had lost 10 out of 12 pregnancies!

“Familial Pregnancy Associated aHUS and Acute Heart Failure successfully treated by eculizumab” by Java et al  and the story of the  “Sisters from  Missouri ”is a message from ASN Kidney Week that is both  timely and exemplary of the theme linking the recent postings on the alliance website about the genetics of aHUS.