Protocol for Treatment of Atypical HUS

[Bill Biermann]

 

 I wanted to describe in a "decision tree format "  the thought process used to treat this disease.    (Disclaimer first:  Atypical HUS is a highly variable disease, so each case must be carefully managed based on the symptoms present).  The basic idea is this:   In the short term, treat the symptoms as they pop up, try to anticipate the issues, but it is a highly reactive process for the most part.  In the long run, find the root cause, and devise a strategy to deal with the long run effects.

 

Short Term Strategies: 

So you heard the words "Your have Atypical HUS".  what does that mean?   The disease has a wide variablity, so the simply answer is "it depends".    Quite often, there is a somewhat severe onset, wtih the most common symptoms being Flu-like in appearance.  A simple blood panel shows low platelets, low Hemoglobin and Hematocrit.   Creatine may or may not be affected early on, although BUN and LDH are frequently out of the normal range.   

The most common initial treatment used is plasma exchange.   Plasma infusiions are effective in same cases, plasma Pheresis in effective in some cases, but there are cases in which neither appear effective (we will see why later).   The plasma treatments simply replenish the patients blood with a necessary protein, a protein that is not being produced properly.

Other short term measures that occur are more supportive in nature.  They include:

-Short term dialysis

-Blood pressure regulation A

-Infection prevention ( quite suseptible to line infections).

-Fluid Control

 

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.  Its degree of activity is unknown, but there is some evidence that suggest the disease may be active, perhaps varying by individual.

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

First Long term strategy - (for low frequency cases)

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.  So you must obtain genetic testing (offered by the University of Iowa) in order to determine the "root" genetics underlying the disease.  

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, or Factor H related  gene problem, then kidney transplantation historically has not been 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, or factor H related.   "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" ( really a MAC attack by the Complement system)  just as the old kidney was by the protein defect.

Over the past two years, a new Complement inhibitor drug has been used to treat Atypical HUS.  The drug Soliris, or Eculizimab,  has shown great promise in treating a multitute of genetic mutations, and even has been effective some some cases of unknown genetic origin.   Currently in evaluation by the FDA, the drug has passed thru 2 clinical trials, with significant results.   As of August of 2011, this treatment appears to offer the most life changing approach to dealing with this disease.

 

The University of Iowa has developed a protocol for patients that are considering the use of Soliris, even those on Dialysis.   The protocol calls for using Plasma Pheresis and Soliris preemptively before a transplant, followed by continuous use of Soliris post transplant. 

 

 

 

 

 

 

 

[Len Woodward]

Hello Bill

Very interesting.

Would like to see it as a decision chart to show the complexities.
Have a question about the pre transplant

administration of eculizumab , would it be a build up or just a one off .Would it vary with living donor or not? 

[Phyllis Ann Talbot]

Len,

I can jump in with our experience - my son Hyde had a kidney transplant along with Eculizimab in February of this year.  He had his first dose 2 weeks prior to transplant, then another dose the day prior, one the day after, one the week following and then every 2 weeks since then.   We did do a living donor so were able to have this luxury, I know of at least one other that did a cadaver kidney and they just started the Eculizimab as they were prepping for the surgery and then followed similar protocols after.  Hope this helps a bit?

[Cheryl Biermann]

Hi Len,

 

Our son, Nathan, had the same protocol as Hyde, living donor as well, he didn't skip to once every two weeks as fast, I think we did one a week for two weeks after discharge then we just had our first once every two weeks this past Tuesday.  Labs were great we did need follow up labs today, (his anti-rejection med was changed), but all his stuff came back great!

Phyllis Ann Talbot said:

Len,

I can jump in with our experience - my son Hyde had a kidney transplant along with Eculizimab in February of this year.  He had his first dose 2 weeks prior to transplant, then another dose the day prior, one the day after, one the week following and then every 2 weeks since then.   We did do a living donor so were able to have this luxury, I know of at least one other that did a cadaver kidney and they just started the Eculizimab as they were prepping for the surgery and then followed similar protocols after.  Hope this helps a bit?

[Len Woodward]

Hello Phyllis and Cheryl
Thank you for letting me know your experience. I hope Hyde and Nathan continue to thrive.

I guess there wil be some families who no longer have the living donor option having had a aHUS recurrence
 in their first attempt.

Perhaps it is too early to know the efficacy of the restricted eculizumab dosage for a cadaver based transplant.

Len


Cheryl Biermann said:

Hi Len,

 

Our son, Nathan, had the same protocol as Hyde, living donor as well, he didn't skip to once every two weeks as fast, I think we did one a week for two weeks after discharge then we just had our first once every two weeks this past Tuesday.  Labs were great we did need follow up labs today, (his anti-rejection med was changed), but all his stuff came back great!

Phyllis Ann Talbot said:

Len,

I can jump in with our experience - my son Hyde had a kidney transplant along with Eculizimab in February of this year.  He had his first dose 2 weeks prior to transplant, then another dose the day prior, one the day after, one the week following and then every 2 weeks since then.   We did do a living donor so were able to have this luxury, I know of at least one other that did a cadaver kidney and they just started the Eculizimab as they were prepping for the surgery and then followed similar protocols after.  Hope this helps a bit?

[Dana M Simone]

Hi Len,

 

My son had a cadaver kidney transplant this past June.  He received his first dose of Eculizimab just hours prior to the surgery. I believe the second dose was 24 hours later, and then once per week for couple of weeks, and every 2 weeks since.

[Len Woodward]

Thanks for your experience Dana , that suggests that by week 4 the dossage is about  the same.

 

[Bill Biermann]

Len

 

Living donors are preferred, because you can plan the administration of the drug using a preferred protocol.  However, that does not rule out a cadaver kidney, it only makes the  protocol a bit compromised, but not to a significant degree.   I'd contact the Univerity of Iowa Nephrology department for more details.

 

Bill

Len Woodward said:

Thanks for your experience Dana , that suggests that by week 4 the dossage is about  the same.