Treatments - Symptoms

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Atypical HUS Treatments

There is no cure for Atypical HUS. In fact, there is no standard treatment, as each case is different.
Children with atypical HUS are in a life threatening situation, but if supportive treatment is administered early and often, they have a good chance of thriving.  

Unfortunately, children with Atypical HUS frequently develop complications. These complications may be:
--Recurrance
--Kidney failure
--Seizures/Neurological problems
--No response to supportive treatments
--Return of Atypical HUS even after s kidney transplant occurs
--Severe Hypertension (high blood pressure) .

BEWARE OF SOME OF THE OLDER STATISTICS !!

You may be frighened out of your mind if you read some older websites which quote very high Mortality rates.  While Atypical HUS is a very frightening disease, death rates are falling considerably, and should continue to do so.  The reason for the better success is the more proactive approach MDs are using.  Also, kidney removal is an option that is a last resort, but kidney removal will get rid of all symptoms.  Of course, once you lose your kidneys, you will be on dialysis.  Losing your kidneys is very serious, so removal is a last resort.

However, children with atypical hus frequently expereince a gradual decrease in kidney function over time, and may "lose" the use of the kidney without removal.  In about half of the cases, the kidneys can be saved.   

Therapy is supportive

There are two types of treatment plans that should be developed.

A Short term plan and 

A Long Term plan .

The Short Term

In the short term,  the symptoms are analyzed and a treatment plan is developed. (Through the years, Nephrologist have tried various drugs that interfere with clotting, drugs that interfere with platelet function steroids, IVIG and a host of other things..).   
The best therapy is to closely monitor the disease, and provide standard supportive techniques to control blood pressure and minimized the damage to kidneys thru plasma infusions, blood tranfusions and/or Plasma Pheresis or plasma exchange.  Early dialysis may be life saving until the kidney function is able to return to normal.  Blood treatments include Red Blood cell transfusions,  Plasma infusions (plasma is the liquid part of the blood), and plasmapheresis (a blood filtering process).
Recurring cases must be watched very closely, and immediate treatment should begin to prevent another full blown Atypical HUS episode.  (We will explain elsewhere why plasma words well)

The Long Term

First, lets state the worse case.  Kidney removal may be necessary (as a very last resort) in order to save the patients life. This is called a nephrectomy.   When the kidneys are removed, quite often, all of the symptoms of the disease go away.  Of course, the disease really does not go away.  But there are no organs left that the disease can affect.

Assuming the kidneys are still present, there are two major ways to deal with the disease.

First Long term strategy

Be very proactive in applying plasma, Plasma exchange (Pheresis) and any other supportive medicine in order to minimize Atypical HUS attacks.  So save the kidneys, and live with an occasional bout.   This strategy has worked in cases that are not severe.  Some individuals have faced one, two or three attacks in their lifetime, and seem to recover each time.

Second Long Term strategy

If the Atypical HUS attacks are frequent, and significant kidney damage is occurring, your long term treatment options will vary based on the root cause of the Atypical HUS attacks.

If you have been diagnosed with an MCP problem, then the prospects of a kidney transplant are quite favorable. The reason?  MCP is a "protective" coating that lines the vessels of the kidneys.  A normal kidney contains this coating.  An atypical HUS patient does not have this protective coating. So if you receive a new kidney, that kidney will contain the protective MCP coatings.  Therefore, a kidney transplant is a very good option and has a high success rate.

If you have been diagnosed with a Factor H, Factor I, or Factor B gene problem, then kidney transplantation does not appear to be a viable option.  The reason? The Originator of the problem in not really the kidney.  Instead, the problem is caused by a protein made in the liver and dumped into the bloodstream.  That protein is called Factor H, Factor I or Factor B.  "Bad" Factor H, I or B is then responsible for causing a cascading event in the complement system.  The only way to get rid of the "BAD" factors is by supplying "Good" factor H, I or B" via plasma infusions or plasma exchange.   So if you transplant a new kidney, that new kidney will be "attacked" just as the old kidney was by the factor H.

Right now, a radically new idea is being used as a last resort for Factor H, I and B cases.  A double transplant involving the liver and kidneys has been tried on a small group of patients.  Since the defective protein orignates in the liver, translanting results in Factor H or I being produced properly, and can sucessfully "rid" the patient of the disease.  THe new liver makes the proper amount of the factor that is deficient.

A double translant should only be considered in those cases of severe failing health.  Right now, there are several synthetic factors being developed in the lab that one day may replace the factors that are not produced correctly. 

March 2009....A breakthrough

In Late 2008. the Foundation received some very exciting news.  A drug company called Alexion Pharm had developed a drug called Soliris  (eculizumab) for a different disease.  However, the drug has been sucessfully used on two atypical hus patients.   While is is way to early to form an opinion one way or the other, this has accelerated the entire testing process on a Complement Inhibiitor type of drug.

New England Journal of Medicine

Alexion To Begin Clinical Trials of Soliris® in aHUS PatientsCHESHIRE, Conn.--(BUSINESS WIRE)--Jan 29, 2009 - Two separate case reports published today in the New England Journal of Medicine (NEJM) examine the investigational use of Soliris ® (eculizumab), a terminal complement inhibitor developed by Alexion Pharmaceuticals, Inc. (Nasdaq: ALXN), in patients with a rare and severe inflammatory disease called atypical Hemolytic Uremic Syndrome (aHUS). In both cases, physicians observed a significant reduction in the destruction of red blood cells, reduced platelet consumption and improved kidney function following Soliris therapy.

 

Separately, Alexion announced today that it is currently initiating clinical trials of eculizumab in patients with aHUS. Soliris is approved in the United States, European Union, and Canada for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH).Atypical Hemolytic Uremic Syndrome is characterized by hemolysis, thrombocytopenia and clotting of blood vessels (microangiopathy), particularly in the kidney and brain, often progressing to end-stage kidney disease. Like PNH, aHUS is caused by a deficiency in normally occurring complement inhibitors. Typically, patients with aHUS have genetic mutations in one of several complement inhibitor proteins that lead to uncontrolled complement activation. Excessive complement activation may contribute to severe inflammation of the blood vessels and blood clotting through the activation of white blood cells, platelets, and the endothelial cell lining of blood vessels. (1)The prognosis for patients with aHUS is poor. Approximately 70% of patients with the most common mutation experience chronic renal insufficiency, chronic dialysis, or death by one year after the first clinical episode. (2) Following kidney transplantation, recurrent aHUS causes kidney transplant failure in approximately 62 - 88% of patients. (3)Case ReportsIn a case report submitted to the NEJM by Ralph A. Gruppo, M.D., Director of the Comprehensive Hemophilia and Thrombosis Center at the Cincinnati Children's Hospital Medical Center, an 18-month-old infant was admitted to the hospital following a fourth clinically severe relapse of congenital aHUS. During this episode, the patient did not respond to daily plasmapheresis, a procedure whereby proteins are removed from the blood by circulating the patient's blood through a machine. When the patient's condition deteriorated further, the physician administered Soliris. Complete blockade of terminal complement was observed in this patient, and hematologic and renal improvement began within 48 hours after initiation of treatment. Plasmapheresis was discontinued within the first week of eculizumab treatment and clinical remission was sustained throughout the 60 day observation period. The report further notes that eculizumab therapy is ongoing for over four months, to date, with sustained disease remission and no further plasma therapy intervention.“It is well known that aHUS is a devastating disease without effective treatment options,” explained Dr. Gruppo, lead author of the report. “Further, after clinical worsening, there may be virtually nothing a physician can do to prevent further kidney damage and eventual kidney failure. Based on this initial and very limited experience, further studies of terminal complement inhibition with eculizumab are warranted.”In a second case reported in the same issue of the NEJM by Dr. Jens Nuernberger of the Department of Nephrology at University Duisburg-Essen in Essen, Germany, a 37-year-old woman with a history of kidney failure due to aHUS and loss of her first kidney transplant due to recurrent aHUS, was admitted to the hospital with progressive and severe aHUS shortly after her second kidney transplant. The patient's aHUS condition continued to clinically worsen despite extensive plasma treatments, indicating a high probability that the second kidney transplant would fail. After the administration of eculizumab, hemolysis quickly resolved, platelet count rebounded and kidney transplant function recovered. The patient's renal graft function has remained stable.Eculizumab appeared to be well tolerated in these two patients, with safety observations that have been consistent with those reported from controlled trials with eculizumab in patients with PNH."There is a profound need to improve the management of aHUS. We are encouraged by the initial clinical experience with eculizumab in a very limited number of aHUS patients, and we are undertaking prospective clinical trials to investigate the role of complement inhibition in this condition," said Leonard Bell, M.D., Chief Executive Officer of Alexion.Upcoming Clinical StudiesAlexion is currently initiating four prospective, open-label clinical studies of eculizumab as a treatment for patients with aHUS in North America and multiple European countries: two studies of patients who are plasma therapy sensitive (one in adults and one in adolescents) and two studies of patients who are plasma therapy resistant (one in adults and one in adolescents). Information on the trials can be requested by e-mail using the address clinicaltrials@alxn.com, or by visiting the Alexion website at www.alexionpharma.com and clicking on the clinical trials link. The trials also will be posted to the www.clinicaltrials.gov website maintained by the U.S. National Institutes of Health

The Symptoms

In most cases, Atypical HUS does not begin with a violent illness. Instead, the child starts off ill, fatigue, irritable, perhaps has an infection and lethargic to a point where hospitalization is needed. Supportive treatment is absolutely necessary in order to prevent further damage.
(As opposed to Typical or regular HUS, which begins rather violently, with a severe bout of gastroenteritis that may be accompanied by bloody diarrhea).
Thereafter, symptoms of both typical and Atypical HUS may be similar. Atypical HUS causes clotting, and therefore results in vascular enlargement. Clotting tends to affect the kidneys, and may result in acute kidney failure, requiring dialysis or kidney tranplants.
A wide variety of symptoms can occur. Life threatening intestinal problems may occur. Neurological problems such as seizures, blindness and coma could develop (though rarely do). Profound intestinal or neurological diseases are indicative of a more severe HUS, and have poor prognosis.
Atypical HUS patients are especially proned to recurrences of the disease and are much more likely to develop chronic renal failure and other complications such as chronic high blood pressure. Atypical patients can have Atypical HUS episodes set off by routine colds and infections.