Wednesday, December 31, 2014

Rapid Response Team

End-of-year greetings, loyal blog readers. Once again I am publishing the only post for the month with just a few hours to spare. Maybe that will change in 2015. Or maybe not.

Today's post will be another update on Mom, followed by the always exciting monthly blog status update for the end of November. The last update on Mom was in the October 30, 2014 blog post, and there really was not much to update at that time. She had been released from the hospital on September 25 after another GI bleeding episode, and not much had changed since then. She has been feeling very tired after most dialysis sessions, and often would need to take a very long nap in the middle of the day after coming home from dialysis since she goes early in the morning. But she did recently change her dialysis start time from the first time slot in the day to the last, which meant she could get some things done during the day before dialysis and then just come home and go to bed. That seems to be working better.

Since everything was going along smoothly in November it was time for something to happen. Sure enough, Mom had another GI bleeding episode and went to the emergency room the morning of Saturday, November 22. She had been nauseous on Thursday and first noticed some bleeding on Friday before going to dialysis Friday night. Her first hemoglobin measurement at the hospital was 7.8, which was down from 10.2 for the Monday blood draw at dialysis. I got to the hospital shortly after 2 PM to relieve my sister Laura who had taken Mom to the ER that morning, and Mom was admitted and arrived in her room at 2:40 PM. She did not think they were going to give her a blood transfusion based on what she was told in the ER, but one of the first nurses to come into her room mentioned something about a blood transfusion.

Shortly after 3 PM a doctor (Dr. W) from the same office as Mom's general physician came to the room and talked to us. She said it made sense to go ahead and give her a unit of blood because her hemoglobin had dropped so much since Monday which meant she was actively bleeding. Mom and I filled her in on the history of this GI bleeding issue and she asked Mom how she was feeling. Mom said that other than not having any energy she felt fine. No chest pain, no shortness of breath, etc. She asked Mom if she thought she needed oxygen and Mom said she didn't think so. Then they talked about diet and whether or not Mom could eat something. Dr. W looked over the hospital menu and told Mom to wait about 20 minutes to give her time to enter the orders regarding Mom's diet. I checked the time and it was 3:25 PM, so I planned on having Mom order some food around 4:00 PM.

I stayed in the room talking with Mom for awhile, figuring I would leave after Mom ordered her food since everything was stable at that point and there had not been any discussion of doing any tests this evening. At some point Mom mentioned she could tell she was having some heart palpitations, but she was not in any distress and I did not think much of it since I knew one of her medications was for heart palpitations. She was not connected to any monitoring equipment at this point, so I did not have any information about her heart rate. Then my sister Amy called me at 3:54 PM. I talked to her for a few minutes and then handed the phone to Mom so she could talk to Amy. Mom and Amy talked for a few minutes and then Mom handed the phone back to me. I was talking to Amy and telling her I was planning on leaving soon and didn't see any reason for her to come to the hospital tonight when I could see Mom was having trouble getting comfortable in bed. She told me she needed oxygen and to get off the phone.

I got off the phone with Amy and pressed the call button for the nurse. A nurse or technician walked into the room within a few seconds of me pressing the call button (probably just a coincidence) and I told her Mom needed oxygen. She turned right around, I assume to either get someone to do it or to get what she needed to put Mom on oxygen. Mom kept getting worse and said it felt similar to what she experienced on the cruise ship when she couldn't breathe because of the fluid buildup. Ok, we have a bona fide situation now. Then a nurse answered the call button and Mom told her she needed oxygen and she probably said something about heart palpitations or difficulty breathing, I don't remember exactly.

Mom's room was very close to the nurse's station, so a nurse entered the room rather quickly. I immediately told her Mom's symptoms had an acute onset, and with that and whatever she saw going on with Mom she quickly left the room and got some help. I heard someone asking about calling an RRT, which I later learned stands for Rapid Response Team. (It's not as serious as a "Code Blue.") I knew it was about to get crowded in the room, so I got the hospital phone and Mom's cell phone off her bed and stepped into the hallway. As people started filing into the room I heard over the intercom the call for RRT with Mom's room number, and someone entering the room said she was coming in with the crash cart. I also heard a nurse at the nurse's station trying to contact Dr. W.

While I was outside in the hallway I texted and called Amy to keep her informed the best I could, since I had to abruptly end our previous phone call. I could hear Mom talking to the nurses so I knew things weren't too bad. I did hear someone say her heart rate was in the 140s, which is considerably higher than her resting heart rate which I believe is typically in the 60s or 70s.

Sometime after 4:30 PM a nurse told me they were moving Mom from this floor (sixth) to the third floor, which is the telemetry floor. They can monitor her more closely there since those patients are always connected to heart monitors which I assume are monitored centrally, plus they can give more medications on that floor than they can on the sixth floor. So after they wheeled Mom out I gathered up her stuff and went down to that floor. She was settled in her new room just before 5:00 PM.

Mom's pulse rate was 137 bpm when I arrived in that room, and it gradually went down to the 120s as they gave her some medications to lower her blood pressure and pulse. Her blood pressure was fine but her pulse was still above 120 when I left shortly after 7:00 PM. She did order some food and had no difficulty eating it. Her hemoglobin at the 5:00 PM blood draw was 8.0, so it looked like that was stable and she might not need a blood transfusion after all.

Mom sent me a text the next morning (Sunday, November 23) saying her hemoglobin was down to 6.4 and she would be getting a blood transfusion. Her heart rate had finally come down to the 60s after she ate breakfast Sunday morning. She received another unit of blood Sunday night because her hemoglobin was at 6.5. It was up to 8.7 Monday night and still at 8.7 Tuesday morning, so it looked like things were holding. She had dialysis in the hospital Wednesday morning, November 26, and then she was discharged that evening (the day before Thanksgiving.)

Unfortunately we did not learn anything new during this hospital visit, since no imaging tests were done. One of the physician assistants from her gastroenterologist's office did talk to Mom about having another colonoscopy to try to locate the source of bleeding, but Mom questioned whether that was really necessary since the last one didn't show anything and the prep for colonoscopy is so difficult.

If she goes to the hospital again for this GI bleeding issue, our plan is to contact the offices of both her general physician and her gastroenterologist to let them know she is on the way to the emergency room, so hopefully those doctors can get involved as soon as possible and order whatever imaging tests might help locate the source of the bleeding. For the record, here are the dates of her emergency room visits and hospitalizations this year for GI bleeding:

May 2 (ER only, not admitted)
July 30 - August 3
September 18 - September 25
November 22 - November 26

In case you're curious, that was 89, 50 and 65 days between hospital visits, for an average of 68 days. So if nothing changes, the next episode of GI bleeding is due around January 29 of 2015.

Happy New Year!!


=====Monthly Blog Status Update===== 

As of November 30, 2014:


Total posts: 144 (1 in November)

Total pageviews: 21,500 (~800 in November)

Email subscribers: 12 (increased by 2)

Total number of countries that have viewed the blog: 101

No new countries viewed the blog in November.
=====

Wednesday, November 26, 2014

Dallas Support Group Meeting: November 8, 2014

Today's post will be about the Dallas amyloidosis support group meeting Mom and I attended on November 8, 2014. Attendance at this meeting totaled 32 people including the two guest speakers. I counted 17 patients and 13 caregivers/family members/friends. The breakdown by type was seven AL amyloidosis patients, five familial, four localized, and one person who was not typed yet but AA amyloidosis (secondary) was suspected. This was the first meeting for five of the patients, one of whom had ATTR and received a heart transplant just a month ago and seemed to be doing very well. In fact, a recurring theme for this meeting was that several patients are doing much better than they were a year or two ago, and people are surviving longer with amyloidosis. For instance, one of the attendees was an 11-year survivor (since diagnosis) who had a stem cell transplant in 2004. That kind of survival with AL amyloidosis used to be very rare.

The guest speakers were Dr. Zonder from Karmanos Cancer Institute in Detroit and Dr. K from The Binding Site, which is a company that develops blood tests used in the diagnosis and monitoring of AL amyloidosis (and many other similar diseases). Dr. K's presentation went over some of the terminology used in discussing AL amyloidosis, such as heavy chains, light chains, lambda and kappa, and how those are all related, what is important in testing as the disease is monitored, etc. Good info for AL patients, but not really applicable for AFib.

Dr. Zonder's presentation and discussion with patients included a lot of information about emerging therapies being developed and tested for all types of amyloidosis and how they worked. As I understand it, treatments can be divided into three groups:

  1. Treatments that reduce or eliminate the production of the misfolded proteins. This would include stem cell transplants and chemotherapy for AL amyloidosis patients. In the case of fibrinogen amyloidosis, that is what a liver transplant does since the liver produces the mutated fibrinogen proteins.
  2. Treatments that prevent the formation of amyloid deposits.
  3. Treatments that dissolve amyloid deposits once they are formed so they can be eliminated by the body's normal processes. Examples of this would be CPHPC and doxycycline, both of which are in early clinical trials for all types of amyloidosis.

Dr. Zonder also said a few kind words to the group about my blog, since he became aware of it last year and has read some of it. That was nice to hear and it did make my head swell up just a little bit. We got to chat some after the meeting was over, too. I recently discovered that he also gave the blog a mention on his Twitter post later that day. So I guess I'll keep blogging (not that I was thinking about stopping any time soon.)

In the next post we may get to answer the question: What do they serve in the hospital on Thanksgiving Day?



=====Monthly Blog Status Update===== 

As of October 31, 2014:


Total posts: 143 (1 in October)

Total pageviews: 20,800 (~600 in September)

Email subscribers: 10 (no change)

Total number of countries that have viewed the blog: 101

No new countries viewed the blog in October.
=====

Thursday, October 30, 2014

Article Reviews (1996 and 2007) - Early summary, and AFib in Italy

Hello again, loyal and patient blog readers. It is time for another monthly post, and this one will include not one, but two article reviews. As a bonus, at the end of the post you will find the always exciting monthly blog stats.

First, a quick Mom update. There really is not much to update, other than the fact that she has not been hospitalized again and things are more or less stable. It turns out this month was a good month for her to stay out of the hospital because the hospital she was in during her September visit, which is also the hospital closest to her internist and gastroenterologist, is none other than Texas Health Presbyterian in Dallas. You may recall that is the hospital where Thomas Eric Duncan, the first person diagnosed with ebola in the US, was treated. In fact, his first visit to that hospital was the same day Mom was released, which was Thursday, September 25. So yes, for awhile we were wondering what we would do if Mom's bleeding issues came back and she needed to go to the hospital. It was also a little weird watching Anderson Cooper live on CNN broadcasting from in front of that hospital, knowing I could drive to that spot myself in about 20 minutes. Fortunately we did not have to make any hospital decisions and the local ebola drama seems to be fading away.

Today I am going out of sequence with the article reviews to catch up on some older ones I acquired after starting to review articles. Both of these reviews will be rather short.

Title: Five Kindreds With Variant Fibrinogen Presenting Renal Amyloidosis (1)

Authors: T. Uemichi, JJ Liepnieks, MT Hull, MA Gertz, MD Benson (Indiana University, Indianapolis, IN; RLR VA Medical Center, Indianapolis, IN; Mayo Clinic, Rochester, MN)

Journal: Neuromuscular Disorders (1996)

This article appeared in a supplement to the journal "Neuromuscular Disorders" and is just one paragraph (ten sentences.)  It briefly describes the three mutations known at that time to cause fibrinogen amyloidosis. Those mutations were:

  • Arg554Leu (one kindred with three affected members)
  • Glu526Val (three kindreds with a total of 11 affected members)
  • 4904DelG (one kindred with two affected members)

So that is where things stood in 1996, three years after the first article about a fibrinogen amyloidosis mutation was published. Three mutations, five kindreds, and 15 people known to be affected. Although the Glu526Val mutation was not the first one discovered, it did take the lead rather quickly. The next article will give us a sense of how prevalent AFib was in Italy about ten years later.

Title: Renal involvement in systemic amyloidosis  --  an Italian retrospective study on epidemiological and clinical data at diagnosis (2)

Authors: Bergesio, Ciciana, Santostefano, Brugnana, Manganaro, Paladini, Di Palma, Gallo, Tosi, Salvadori (Italy)

Journal: Nephrology Dialysis Transplantation (2007)

This is a much longer article (eight and a half pages, plus one page of references). But my review, which is actually just a summary of the part relevant to us AFibbers, will be shorter than the abstract. This article reports on a study of 373 patients diagnosed with some form of systemic amyloidosis (with renal involvement) in Italy between January 1995 and December 2000. Of those 373 patients, only six were diagnosed with a hereditary form of amyloidosis, and only one of those six patients had a fibrinogen mutation (Glu526Val). There really isn't enough data there to draw any conclusions regarding the prevalence of fibrinogen amyloidosis in Italy, other than to say it was rarely diagnosed before 2007. See, I told you that would be a short review.  ;-)

No, there was not much in this month's blog post but hopefully I can do some more cleanup of the article reviews and get those closer to completion in the next few months. The next blog post should be a report on the Dallas Support Group meeting in November.


=====M
onthly Blog Status Update===== 

As of September 30, 2014:


Total posts: 142 (1 in September)

Total pageviews: 20,100 (~1000 in September)

Email subscribers: 10 (no change)

Total number of countries that have viewed the blog: 101

1 new country viewed the blog in September:

British Indian Ocean Territory**

**The British Indian Ocean Territory is a group of very small islands in the Indian Ocean. However, since the two-letter country code is io (as in input/output), that code is often used by technology companies.
=====

Citations

(1) Uemichi T, Liepnieks JJ, Hull MT, Gertz MA, Benson MD. Five kindreds with variant fibrinogen presenting renal amyloidosis. Neuromuscular Disorders. 1996;6, Supplement 1(0):S35.

(2) Bergesio F, Ciciani AM, Santostefano M, et al. Renal involvement in systemic amyloidosis--an Italian retrospective study on epidemiological and clinical data at diagnosis. Nephrol Dial Transplant. 2007;22(6):1608-1618.

Tuesday, September 30, 2014

Once more unto the breach

Greetings, loyal readers. Once again I have gone a month without a blog post and I really need to get one done before the end of the month. I guess I can still blame it on a summer hiatus, since summer did not officially end until September 22. Anyway, it's time for another Mom update. And be sure to check out the monthly blog stats at the end of this post to see which country was number 100 to visit the blog.

In the last post we learned that Mom had been hospitalized from July 30 through August 3 due to gastrointestinal bleeding, but the source of the bleeding could not be determined. We also learned that Mom has diverticulosis (not diverticulitis), and there is not much that can be done proactively about that. We'll just have to wait and see if she starts bleeding again.

I don't know if it was the blood transfusions or something else, but Mom's hemoglobin started going up toward the end of August and into September. Given her history of anemia this is a good thing, up to a point. Naturally, her hemoglobin went over that point. Normal is 10 or above, and hers got as high as 13.1 on September 8. For a typical person 13.1 is not high, but her nephrologist was concerned because they do not like dialysis patients to have a hemoglobin level above 12.0. He stopped giving her Epogen during dialysis and said if her hemoglobin did not come back down in a week or two they would have to do something about it. (What they would do is just keep some of her blood during dialysis, which causes the hemoglobin level to drop. People with blood disorders such as hemochromatosis that cause high hemoglobin levels have blood drawn periodically to lower their hemoglobin levels.)

Well, we didn't have to wait for Mom to lose some blood during dialysis because her bleeding issue came back over the weekend of September 13 and 14. It wasn't too bad at first, then it got worse, then better, then worse again. On the one hand we did not want to take Mom to the ER for them to do nothing (like the visit in May), but on the other hand we did not want to wait until she became very anemic and was in need of a blood transfusion. She was not feeling very good during dialysis on Wednesday, but she started feeling a little better later in the day and did not think she needed to go to the emergency room.

Then on Thursday, September 18, things started to happen. I got the following text message from one of my sisters just before 7:00 AM:

"Wow! Just pulled up to Mom's house and found 3 fire trucks and ambulance . . . 

Electrical fire 3 doors down and across the street!"

Yes, my heart also skipped a beat when I read that first sentence, before I read and processed the second sentence. Sorry to put you through that. Anyway, later that morning I talked to Mom to see how she was doing and convinced her she needed to go the hospital since things were not getting any better. My sister Laura took her around noon and they took her back to the emergency room fairly quickly. Her hemoglobin was 8.7, down from 12.0 on the Monday morning blood draw at dialysis. She obviously had lost a lot of blood so they admitted her. The next morning Mom sent me a text message saying her hemoglobin dropped to 6.8 that evening so they gave her two units of blood overnight.

I won't go through the play-by-play description of what happened over the next several days, but here is a summary of what happened before she was released from the hospital on Thursday, September 25:
  • They did a few different types of scans trying to pinpoint the source of the bleeding, but none were good enough to really make a decision on what to do.
  • Depending on what the issue is, there are three options to deal with it. Those are:
    1. Repair the bleeding site during a colonoscopy
    2. Repair it using radiology (I am guessing something like aligning x-rays to zap it.)
    3. Surgery to remove the bleeding section of the colon
  • She had a colonoscopy in the hospital on Monday, September 22 but her gastroenterologist was still unable to determine the source of bleeding that would account for the blood loss that was occurring when she was admitted. He said the AVM (arteriovenous malformation) did not look like it had been bleeding. He did see a few blood clots and saw some minor bleeding when he rinsed those away, but those are not a major source of bleeding.
  • Mom and I talked with a surgeon several times about her situation, and he was very good at explaining what they know and don't know. He also explained that they want to rule out all other possibilities before doing surgery, since it is a major surgery to remove some or all of the colon. So we felt good that they would not recommend surgery unless they felt it was the last option.
  • One reason this bleeding issue is so difficult to diagnose is by the time Mom notices the blood she has probably been bleeding for some time, and it may have even stopped. These imaging scans that are used to locate the bleeding tend to produce better results if there are only clear liquids in the colon, but by the time the colon gets clear the bleeding may have already stopped.
  • The day before she was discharged from the hospital they started Mom on a drug called Sandostatin (generic name octreotide), which the nurse told us is a commonly used first line of defense to stop intestinal bleeding. Supposedly it constricts the smaller blood vessels to reduce the chances of bleeding. It is injected into the abdomen, so now Mom has to give herself this shot once per day.

So we really are not much further along with solving this bleeding issue, but maybe this new drug will stop it. All we can really do is wait and see. At least now we know as soon as Mom sees blood she needs to get to the ER to increase the chances of the source being located.

On a sad family note, Mom's older brother Wayne passed away on Saturday, September 27 at the age of 77. He appears to have had a sudden heart attack while out on the tractor at his farm, which is probably the way he would have chosen to go: quickly, while working around the farm. He was never tested for the Afib mutation, but he did have kidney issues and was also diabetic. His descendants consist of one son and two grandchildren.



=====Monthly Blog Status Update===== 

As of August 31, 2014:


Total posts: 141 (1 in August)

Total pageviews: 19,100 (~700 in July)

Email subscribers: 10 (no change)

Total number of countries that have viewed the blog:100!!!

1 new country viewed the blog in August:

Fiji (I wonder if it was Truman Burbank?)
=====

Sunday, August 31, 2014

Capsule Endoscopy

If you were wondering if the blog changed from weekly to monthly this summer you would be right. I didn't plan things that way, it's just the way things worked out. We had a very busy summer and it seems to have gone by very quickly, so we will see what happens with the blog frequency going forward. It is very unlikely I will go a full calendar month without posting, since the Monthly Blog Status Update really needs to published monthly. (Incidentally, you can see at the bottom of this post that the country count almost reached 100 in July. Did we reach 100 in August? Find out in September . . .)

Today's post will be an update on Mom. In the previous update (May 25) I mentioned she had had some GI issues that were causing some blood loss. She had visited a gastroenterologist and had a colonoscopy. The colonoscopy showed that she has an arteriovenous malformation (AVM), which is when the blood vessels do not form correctly, in this case in the inner wall of the colon. It can be corrected during a colonoscopy if it becomes a problem (I assume by cauterizing), but there is no need to do anything at this point.

As of June the plan was to do a capsule endoscopy, which requires the patient to swallow a pill camera which then transmits pictures to a receiver (worn by the patient) as it travels through the GI tract. I thought that was the coolest thing ever and was hoping Mom would get a disc with those pictures like we did in the past for her CT scan. Before they have patients swallow the pill camera they have them swallow a pill the same size as the pill with the camera to make sure it will pass through the patient's GI tract. If the pill camera gets stuck they usually have to remove it surgically, whereas this test pill will dissolve on its own if it does get stuck. Mom swallowed the test pill at some point in July and it did not get stuck, so at that point it was just a matter of scheduling the appointment to swallow the pill camera.

On Wednesday, July 23 I found out Mom had been having some bleeding issues for three days. She told her nephrologist about it that morning, but her hemoglobin (from Monday's blood draw) was over 11 so he was not overly concerned and did not consider it an emergency situation. Mom called the office of her gastroenterologist and told them what was going on, but the earliest they could see her was August 4 to swallow the pill camera. So given all that, and the fact that Mom did not feel bad and things were improving, we decided there was no need to take her to the emergency room and have a repeat of the visit in May where they basically did nothing.

Oh, what a difference a week makes . . .

The following Wednesday (July 30), Mom arrived for dialysis and was told that instead of having dialysis she needed to go to the hospital as soon as possible because her hemoglobin (from the Monday, July 28 blood draw) was 5.5 and she needed a blood transfusion. So she went to the hospital and they ran whatever series of tests are required before giving someone a blood transfusion. Her hemoglobin measured at the hospital was 4.6, so it had dropped a little since Monday. She was admitted and started getting the transfusions. They also did an abdominal scan of some sort to determine the source of the bleeding.

There was some more bleeding overnight Wednesday night, which Mom was able to show to the nurses. She had dialysis in the hospital Thursday morning and also received some more blood. Her hemoglobin increased to 9 on Thursday, so the doctors were pleased with that and she did not receive any more blood transfusions. We do not know exactly how many units of blood she received, but I think it was 4 to 6 units. (I was out of town during all this excitement, so I was getting all my info second- and third-hand.) The scan that was done on Wednesday did not show any active bleeding, so they started the capsule endoscopy on Thursday and had her swallow the pill camera. One of my nephews told Mom she was taking the ultimate selfie.

On Friday, August 1 they gathered the equipment for the pill camera but said it would take a couple of days to go through the pictures. They told Mom she would still be in the hospital for dialysis on Saturday, and later in the day she was told she would be there all weekend and would not be leaving until they determined the source of the bleeding.

On Sunday my son and I traveled back home from North Carolina, and we were planning on visiting Mom in the hospital after we went home and took care of some things. I contacted Mom after we arrived at the airport, and much to my surprise she was already home. The doctor (not her normal gastroenterologist but another one from the same practice) said there were no obvious sources of bleeding found in the pictures from the pill camera, and since her hemoglobin was up and there was no active bleeding, there was no need to keep her in the hospital. He said they would probably schedule a colonoscopy to see if they could find the source of the bleeding. He also said something about Mom having diverticulitis, which was news to her.

The next week Mom scheduled an appointment with her gastroenterologist (Dr. H) for August 15, and fortunately I was able to go with her due to my work schedule that day. Here is what we learned from Dr. H:

  • He has essentially ruled out cancer or any other life-threatening condition as being the cause of the bleeding.
  • Mom has diverticulosis, not diverticulitis. Diverticulosis is when outpockets form in the wall of the colon, and often they do not cause any problems. But if they get infected and form abscesses, that is called diverticulitis and it can be serious.
  • Mom's AVM (Arteriovenous Malformation) is near the beginning of the large intestine (colon), above the appendix. He did not see any sign of bleeding there in the pictures from the capsule endoscopy.
  • The pictures did show some blood in the colon about 30 minutes after the camera passed the AVM (probably in the transverse colon at that point), but the source of the bleeding could not be determined.
  • There isn't much to do at this point since there is no active bleeding. If another bleeding episode does occur and the source can be pinpointed, it may be possible to remove that section of the colon.


So right now there is not anything to do proactively, other than try to maintain a high fiber diet. Dr. H said some people just have one bleeding episode and then no more, whereas other patients continue to have bleeding episodes until something is done to correct them.

One final note about the blood transfusions. Mom and I both remember when she had some appointments for her initial evaluation for the kidney transplant, someone told us that having a blood transfusion could have some impact on a person's eligibility for kidney transplant. We did not know if it was an automatic exclusion, if it was dependent on some test they do after a blood transfusion, or something else. I spoke to Mom's transplant coordinator this past week and asked her about it. She said blood transfusions cause a patient to develop additional antibodies, and that can have an effect on whether or not a specific kidney is a good match. So it just means they have to be slightly more selective when determining whether or not a potential donor kidney is a good match for her.

Next up I hope to get back in the groove and continue with the article reviews.

=====Monthly Blog Status Update===== 

As of July 31, 2014:


Total posts: 140 (1 in July)

Total pageviews: 18,300 (~1000 in July)

Email subscribers: 10 (no change)

Total number of countries that have viewed the blog: 99

2 new countries viewed the blog in July:

Burundi
Tunisia
=====

Saturday, July 12, 2014

Article Review (2012) - Solid organ transplantation for non-TTR hereditary amyloidosis: report from the 1st International Workshop on the Hereditary Renal Amyloidoses

Today's article under review expands a bit on the topic of organ transplantation that was discussed in a previous article (reviewed in the May 4, 2014 blog post), and it has the first mention of milestone in the treatment of fibrinogen amyloidosis.

Title: Solid organ transplantation for non-TTR hereditary amyloidosis: report from the 1st International Workshop on the Hereditary Renal Amyloidoses (1)

Authors: Arie J. Stangou, Luisa Lobato, Steven Zeldenrust, Mohamed Rela, Bernard Portmann, Reinhold P. Linke, Isabel Conceicao, Gerd Otto, Henryk Wilczek, Ole Suhr, Daniel Azoulay, Gilles Grateau, Maria Picken, John O’Grady, Nigel Heaton, Bo-Goran Ericzon, Merrill D. Benson (UK, Portugal, US, Germany, Sweden, France)

Journal: Amyloid (2012)

Abstract: 
Fibrinogen A alpha-chain (AFib) and apolipoprotein AI (AApoAI) amyloidosis due to variants in the AFib and ApoAI genes are the most common types of hereditary amyloidosis in Europe and the United States. Liver is the exclusive source of the aberrant amyloidogenic protein in AFib and responsible for supplying approximately half of the circulating variant ApoAI. Nephrotic syndrome and renal impairment due to renal amyloidosis are common disease manifestations; however, recent research provides evidence to support a more diverse and systemic disease phenotype, which in turn has implications in the management of the hereditary amyloidoses with solid organ transplantation and, in particular, liver transplantation.
Here is a link to the article (not free) if you would like to follow along:  http://informahealthcare.com/doi/abs/10.3109/13506129.2012.668503



As stated in the abstract, this article discusses the use of organ transplantation (primarily liver) in the treatment of fibrinogen and apolipoprotein amyloidosis. This review will focus on fibrinogen amyloidosis.

The article begins by stating that the use of organ transplantation in the treatment of transthyretin-related amyloidosis (ATTR) has been widely studied, in contrast to the use of organ transplantation in the treatment of non-TTR amyloidosis types, such as fibrinogen, apolipoprotein, lysozyme and gelsolin. That fact becomes obvious when comparing the number of transplants reported to the FAP World Transplant Registry (http://www.fapwtr.org/) for ATTR vs. the non-TTR mutations.

If you think there is a mistake in the first sentence of the abstract, you are correct. The word "renal" is missing. It should state that ". . . amyloidosis due to variants in the AFib and ApoA1 genes are the most common types of hereditary renal amyloidosis in Europe and the United States." The beginning of the section on fibrinogen amyloidosis does state that fibrinogen amyloidosis is the most common form of hereditary renal amyloidosis in the UK, Ireland and the US.

Some of the basic characteristics of fibrinogen amyloidosis (AFib) are presented, specifically:


  • Six different mutations, with the most common being Glu526Val
  • Amyloid deposits consist solely of variant fibrinogen (no wild-type)
  • Patients typically progress to end stage renal failure within 1 to 5 years of presenting with proteinuria and hypertension.
  • In the past, AFib has been regarded as solely nephropathic (affecting the kidneys)

The article then makes the case that fibrinogen amyloidosis is a systemic disease, with reported fibrinogen amyloid deposition in the heart, spleen, vessel walls, abdominal fat, and gastrointestinal tract, in addition to reports of cardiovascular disease and autonomic neuropathy. A series of nine pictures of biopsy slides showing AFib deposits in various organs are shown on this page of the article.

Transplant outcomes are then discussed. Outcomes of isolated kidney transplantation are poor due to rapid recurrence of amyloid in the transplanted kidney. On the other hand, combined liver and kidney transplantation (LKT) is curative but poses significant transplant risks, especially in patients who have been on dialysis for a long time. It is preferred to perform LKT in patients before they begin dialysis. At the time this article was published, twelve cases of combined liver and kidney transplantation for fibrinogen amyloidosis patients had been reported to the FAP World Transplant Registry, with ten of those performed in the UK and two in the US.

The article then mentions that when patients have received a combined liver and kidney transplant before going on dialysis, their residual native kidney function (the remaining function of the patient's original kidneys that are not removed during kidney transplantation) has been salvaged. (That situation was described in greater detail in the 2010 article by Stangou, et al, reviewed in the February 21, 2014 blog post.) This data encourages evaluation of isolated liver transplantation early in the course of the disease to prevent progression to end stage renal failure. Then we have this sentence, informing us that it has, in fact, been done: "The first preemptive isolated liver transplant for AFib was carried out successfully in an AFib patient with moderate renal impairment at the San Francisco Liver Transplant Unit in 2011 (personal communication)."

For those of you who don't know, that patient was our very own Cathy T., who received a liver transplant exactly four years ago today, on July 12, 2010. (Not 2011 as stated in the article.) She was blogging about her experience at the time, so if you want to read about her journey you can start with the first post or jump right to the date of her transplant. She has not blogged in a few years, probably because she is too busy enjoying her bounty of grandchildren which I believe was approaching 20 when Mom and I saw Cathy and her husband at the Familial Support Group meeting in Chicago in October of 2013.

We have seen a few articles suggest an isolated liver transplant may be appropriate for AFib patients who still have a moderate amount of kidney function (GFR above 50 is often given as a recommendation). As you can see from some of Cathy's data near the bottom of the Patient Timelines page, her GFR was considerably lower than that, somewhere between 20 and 30 at the time of her liver transplant. In spite of that, she did receive a liver transplant just before the need for dialysis. (She was also part of a domino transplant, which means her liver was transplanted into another patient.) If she had waited for a liver and kidney transplant, she very likely would have needed dialysis before receiving that transplant.

Cathy's kidney function did improve to some extent after her liver transplant, such that she was no longer eligible for a kidney transplant. My understanding is that even after the source of the amyloid is removed, improvement in kidney function is slow and limited due to the scar tissue that develops. So she is living with the issues that go along with having reduced kidney function, and although her kidney function will likely never get back to "normal," here we are four years post-transplant and she still has not needed dialysis or a kidney transplant. The results of this one case certainly support the suggestion that an isolated liver transplant will halt the progression of fibrinogen amyloidosis. I would expect a patient with more kidney function remaining (higher GFR) at the time of transplant to fare even better.

As far as I know, Cathy is still the only fibrinogen amyloidosis patient to receive just a liver transplant. And I believe this article is the only mention of her transplant in the medical literature to date. Hopefully her case will be published at some point, but until then, if anybody out there is in a similar situation such that an isolated liver transplant is being considered, know that it has been done and it did appear to halt progression of the disease.

This article does give us another way to look at how rare fibrinogen amyloidosis is and how late the diagnosis is, since there had been only 12 combined liver and kidney transplants (and one isolated liver transplant) performed on AFib patients at the time this article was written. That is less than one per year since the first description of a fibrinogen amyloidosis mutation was published in 1993. Going forward, earlier diagnosis in relatives of AFib patients should lead to more cases in which a liver or combined liver and kidney transplant is a viable option. On the other hand, if one or more of the drug treatments under development reduce or eliminate the need for organ transplants in AFib patients, there may be very few additional liver or liver-kidney transplants. Indeed, the times they are a-changin'.


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Citation:

1. Stangou AJ, Lobato L, Zeldenrust S, et al. Solid organ transplantation for non-TTR hereditary amyloidosis: report from the 1st International Workshop on the Hereditary Renal Amyloidoses. Amyloid. 2012;19 Suppl 1:81-84.


=====Monthly Blog Status Update===== 

As of June 30, 2014:


Total posts: 139 (1 in June)

Total pageviews: 17,200 (~1200 in June)

Email subscribers: 10 (no change)

Total number of countries that have viewed the blog: 97

3 new countries viewed the blog in June:

Jamaica
Libya
Luxembourg
=====

Tuesday, July 1, 2014

Dallas Support Group Meeting: June 7, 2014

Wow, once again it has been a long time between posts. I really need to get at least one sent in June so I can include the blog stats for the month of May. I know it will already be July for some of you when I send this post, but at least it is still June for me. Once again I don't have any great excuse for not writing a blog post sooner, but there have been two major projects on the home front that I have been focused on over the last two months. Both of those projects have reached major milestones recently, so hopefully I can get back to regularly writing a post somewhere between weekly and monthly.

Rather than the article review I have been promising, today's post will cover the local amyloidosis support group meeting Mom and I attended on June 7, 2014. Oddly enough, this was my first local support group meeting since June of last year, due to visitors during the November 2013 meeting and my traveling during the March 2014 meeting.

Attendance at this meeting totaled 29 people, including the two guest speakers. By my count there were 16 patients and 11 caregivers. Counting me and Mom there were seven familial patients, with two of those patients from a single kindred in which 17 family members have tested positive for the mutation. There were also five patients with localized or suspected localized amyloidosis. That leaves four patients with AL amyloidosis (plus a caregiver for someone who was not there). So there were more familial than AL patients at this meeting, which is a first for me. Go Familial!!

One of the AL patients was only 34 years old, but doing much better than he was at the November 2012 meeting when he was in a wheelchair. He is walking fine now, and it was good to hear him and his wife discuss the activities he can now do post-recovery. One of those activities is apparently making babies, since they have a child under the age of one now.

One of the guest speakers was from Prothena, and he discussed the NEOD001 trial which is for patients with AL or AA amyloidosis. I did not take any notes during that presentation since it does not apply to fibrinogen amyloidosis, but it was interesting to hear him describe what the drug is actually doing at the molecular level.

The other guest was Dr. S from Mayo Clinic in Jacksonville. He did not give a prepared presentation, but his format at these meetings is to have the patients voluntarily present their cases to him and ask questions, and then he uses the specifics of each case to give short presentations or lessons on the various types of amyloidosis, treatments, methods of diagnosis, etc. Since part of these meetings is usually reserved to go around the room and have everyone present their case to the group, I thought this was a good way to incorporate some of that into the doctor's presentation while he had the floor.

So that's about it for this post, other than the monthly blog stats at the end. Next up, some time in July, will be the next article review.


=====Monthly Blog Status Update===== 

As of May 31, 2014:


Total posts: 138 (2 in May)

Total pageviews: 16,000 (~1500 in May)

Email subscribers: 10 (no change)

Total number of countries that have viewed the blog: 94

4 new countries viewed the blog in May:

Bahamas
Kazakhstan
Malta
Paraguay
=====

Sunday, May 25, 2014

Re-listing

Hello again, loyal readers. It has been much longer than usual between posts, and I don't have any good excuse for not posting. Maybe I just got a temporary case of writer's block. But no need to worry, everyone is fine here.

Today's post will be an update on Mom, and I plan on resuming the article reviews in the next post. We finally have some good news regarding her kidney transplant status. We found out on May 13 that Mom was approved for returning to the waiting list for a kidney transplant on Friday, May 9. The wait for that news took almost two months longer than expected, but at least Mom was still accruing time on the wait list because she was initially approved for a kidney transplant (living donor only) in August of 2012. So now it is a waiting game. Based on the statistics for this transplant center, her wait time going forward may be about a year. But she did agree to receiving a kidney from an extended criteria donor, which is a donor who is older or possibly had some hypertension. It is still a good kidney for transplant but is not considered to be among the very best. In theory that should shorten her wait time.

In the previous update I also mentioned some GI issues Mom was having that were causing some blood loss. Her hemoglobin had also been dropping, likely as a result of the blood loss. Her nephrologist was getting concerned that she might need a blood transfusion if it got too low, so they were watching her hemoglobin very closely. This drop in hemoglobin was likely contributing to her feeling even more tired than normal on the days she has dialysis. Since then she has seen a gastroenterologist and had a colonoscopy and an endoscopy. Some issues were found (nothing serious) and the blood loss seems to be under control now. Her most recent hemoglobin reading was 9.4 (normal is 10 or above), so that appears to be headed in the right direction.

That's all for now. Next up is a review of an article that mentions a milestone in the treatment of fibrinogen amyloidosis.

Sunday, May 4, 2014

Article Review (2012) - The role of liver transplantation in the hereditary amyloidoses: the UK experience

Before getting to today's article review I want to give an update on Mom. As of the previous update (April 5, 2014) we were waiting to hear something about her status regarding the kidney transplant waiting list. Well, here it is a month later and we are still waiting. Mom's nephrologist sent the transplant coordinator an email on Friday, May 3, asking about it. The coordinator wrote back and was nice enough to copy me and said she was planning on presenting Mom's case to the committee on Wednesday, May 7, which is just a few days away. So that is good news. She also mentioned that she needs Mom's latest mammogram results, which of course was news to us. That doctor's office was closed Friday afternoon, so hopefully we can get those records sent over in time so we do not have any more delays.

We had some more excitement on Friday as well. Mom told her nephrologist about some recent symptoms she has been having (gastrointestinal issues), and he recommended she go to the emergency room if those symptoms continued because it could mean Mom is losing a lot of blood somewhere. So Mom went to the emergency room Friday afternoon, but they did not really do much. On the plus side, the ER doctor told Mom that she is being dialyzed very well because most of her lab work looks very good (other than the things that indicate kidney failure, like elevated serum creatinine). She ended up staying about four hours before they released her with instructions to see a gastroenterologist about the GI issues. We will see how that situation develops.

Today's article is the second of two abstracts from the 2012 XIIIth International Symposium on Amyloidosis, which was held in May of 2012 in Groningen, The Netherlands. This abstract is very similar to the abstract I reviewed in the March 28, 2014 blog post, so I will not spend much time on it. If I had been looking ahead a little better I probably would have combined the two reviews into one blog post.

Title: The role of liver transplantation in the hereditary amyloidoses: the UK experience

Authors: A. J. Stangou, B. Gunson, P. Ashcroft, D. Mirza, M. Rela, J. O'Grady, N. D. Heaton, P. Mulesan (Queen Elizabeth Hospital, Birmingham, UK; King's College Hospital, London, UK)

Abstract:
We evaluated the role of liver transplantation (LT) in the hereditary amyloidoses and present the UK experience of LT for fibrinogen A-α chain (AFib), apolipoprotein apoAI (AApoAI) and lysozyme (ALys) amyloidosis. Ten patients with E526V AFib amyloidosis and renal failure received combined liver and kidney transplant (LKT). The combined transplant procedure was curative but associated with significant perioperative risk. Three patients received LKT for AApoAI amyloidosis with renal and liver failure. All maintain normal dual graft function and have exhibited systemic amyloid regression. Two siblings with hepatic amyloidosis in association with ALys (Asp67His) received emergency LT for spontaneous liver rupture. The first patient survived 12 years, while the second remains well with normal graft function at 7 years. Liver transplantation may be curative in AFib, has a role of life-saving treatment in hepatic failure due to ALys, and is reserved for the indication of end-stage amyloid liver disease in AApoAI.

Here is the link to a PDF file with all of the abstracts for the 2012 symposium, if you would like to follow along. This abstract is on pages 415 - 418:  http://www.amyloid.nl/Files/Proceedings%20book%20Amyloid%202012%20voor%20web.pdf

Although this article covers amyloidosis due to fibrinogen, apolipoprotein and lysozyme, I will only discuss the fibrinogen amyloidosis patients in this review. As stated in the abstract, this article reports on ten fibrinogen amyloidosis patients who received combined liver and kidney transplants in the UK. The abstract from 2011 which was reviewed in the March 28, 2014 blog post reported on nine transplant patients (through 2010), so the current article, which covers the period from 1993 through 2011, includes one more patient. Here are the highlights of those results:


  • 7 of the ten patients were still alive after a median follow-up of 76 months (range 9 to 172 months). So one patient was still alive 14 years post-transplant.
  • The three non-surviving patients died during the perioperative period, which includes preop, surgery and recovery. Those three patients were either older or had been on dialysis for a long time.
  • All survivors except one have normal function in the transplanted kidney with no signs of amyloid.
  • Two patients who received transplants before starting dialysis have retained stable function in their native kidneys at 7 and 8 years after transplant.

Regarding fibrinogen amyloidosis, this article also covers two other important points:


  • There were various cardiovascular findings in some of these patients, although none met the criteria for cardiac amyloidosis. These findings were previously reported in the 2010 article by Stangou, et al, which was reviewed in the February 21, 2014 blog post, so I will not cover that again here.
  • Since the liver is the sole source of fibrinogen, a liver transplant appears to be curative for fibrinogen amyloidosis. The authors state their support of the evaluation of isolated liver transplantation in AFib patients with early evidence of renal involvement.

=====

So we do not get much new information from that article, but it does reiterate some important points we have previously seen regarding transplants for fibrinogen amyloidosis patients.


  • Combined liver and kidney transplant is curative because it eliminates the source of the mutant fibrinogen and it restores kidney function. Long term results of those patients who survive the perioperative period are promising.
  • Combined liver and kidney transplantation has increased risk for older patients and those who have been on dialysis for a long time. (The article does not define what a "long time" is.)
  • Some doctors support isolated liver transplantation for fibrinogen amyloidosis patients early in the course of the disease.


The next article up for review is a very thorough discussion of organ transplantation for fibrinogen and apolipoprotein amyloidosis. It mentions something previously unreported in the medical literature, so stay tuned . . .


=====Monthly Blog Status Update===== 


As of April 30, 2014:


Total posts: 136 (4 in April)

Total pageviews: 14,500 (~1000 in April)

Email subscribers: 10 (no change)

Total number of countries that have viewed the blog: 90

2 new countries viewed the blog in April:

Malawi
Sint Maarten (The Dutch portion of the island of Saint Martin)
=====

Saturday, April 26, 2014

Article Review (2012) - Renal amyloidosis associated with a novel fibrinogen A alpha chain (Afib) mutation

Today's article under review brings us to the year 2012, and it is the first of two abstracts I will be reviewing from the 2012 XIIIth International Symposium on Amyloidosis. The 2012 symposium was held in May of 2012 in Groningen, The Netherlands, which was also the site of the first International Symposium on Amyloidosis in 1967. These symposia are now held every two years, which means there should be one in 2014. And as some of you know, it is being held April 27 through May 1 in Indianapolis, Indiana, hosted by our very own Dr. Merrill Benson. Here is the link to the web site for this year's symposium:  http://www.amyloidosis.nl/indpls/indpls_index.html.

Wow, I just discovered the symposium book is available to download from that site (go to the Program page), and it seems to have all of the abstracts that will be presented. The word "fibrinogen" is in there at least 14 times, so there might be some interesting abstracts for those of you who want to read ahead. I will likely be reviewing one or more of those articles in the blog in a couple of months. Ok, back to today's abstract . . .

Title: Renal amyloidosis associated with a novel fibrinogen A alpha chain (Afib) mutation

Authors: Yvonne A. Efebera, Dorota Rowczenio, Anjali Satoskar, Don M. Menson, Tobor Nadasdy, Philip N. Hawkins (The Ohio State University; National Amyloidosis Centre, London, UK)

Here is the link to a PDF file with all of the abstracts for the 2012 symposium, if you would like to follow along. This abstract is on pages 413 and 414:  http://www.amyloid.nl/Files/Proceedings%20book%20Amyloid%202012%20voor%20web.pdf

This abstract describes the case of a man diagnosed with mild renal insufficiency in 1998 and mild proteinuria in 2005. In October of 2011, at the age of 80, his kidney problems had worsened to the point where his serum creatinine was 5.95 mg/dl and proteinuria was 6379 mg/day. He had no other significant symptoms, and his past medical history included high blood pressure and high cholesterol, both of which were under control. He had no family history of renal disease. His parents were Russian and died at age 72 and 75.

A kidney biopsy showed amyloid deposits in the glomeruli that stained strongly for fibrinogen, and DNA analysis showed this patient had a previously unreported fibrinogen mutation. This mutation was also at position 526, like the most common fibrinogen amyloidosis mutation, Glu526Val. But instead of substituting Valine for Glutamic acid, this mutation substituted Lysine for Glutamic acid. So this mutation would be written as Glu526Lys (or E526K instead of E526V). (For the uber-curious readers: The GAG for Glutamic Acid was changed to AAG for Lysine in this mutation.)

The abstract states that the clinical presentation for this patient was indistinguishable from that of a patient with the Glu526Val mutation, and the amyloid deposition in the biopsy was similar. One major difference between the two mutations is that this patient is of Russian ancestry, whereas the majority of patients with the Glu526Val mutation are of European ancestry.

=====

This mutation is the first new one reported in the literature since the 2009 article by Gillmore, et al (the study of 71 patients) reported on four new mutations. It is interesting that this mutation occurs at the same point as the Glu526Val mutation. As stated in the article, the symptoms of this patient were the same as what we would expect in a patient with the Glu526Val mutation. The symptoms did appear later in life and progress more slowly than we typically see in patients with the Glu526Val mutation, but we cannot draw any conclusions from a single case.

The article did not state whether or not this patient had any offspring, and it did not mention any other relatives. It will be interesting to see if this mutation appears again in the literature, either in this same kindred or a different one.

Next up for review is another abstract from the 2012 symposium which revisits the topic of organ transplants.


Saturday, April 19, 2014

Article Review (2011) - Long-term follow-up of patients with hereditary fibrinogen A alpha-chain amyloidosis

Today's article review concludes the Portugal series, which started with the April 5, 2014 blog post on a 2004 article describing the first fibrinogen amyloidosis case in Portugal. Then the April 12 blog post covered two abstracts about Portuguese patients (2005 and 2008), and we learned about a cluster of patients concentrated in northern Portugal. Today's article from 2011 reports on this same cluster of patients.

Title: Long-term follow-up of patients with hereditary fibrinogen A alpha-chain amyloidosis (1)

Authors: I. Tavares, L. Lobato, L. Moreira, J. Santos, P. Lacerda, J. Pinheiro, P. Costa (Various institutions in Portugal)

Journal: Amyloid (2011)

Abstract:
Fibrinogen A alpha-chain amyloidosis (AFib) is an autosomal dominant condition with variable penetrance, usually of late onset. Progression to stage V chronic kidney disease is a consistent feature. There is a cluster of AFib in the district of Braga, Portugal, characterized as a systemic disease with a high penetrance.

Here is a link to the article (not free) if you would like to follow along:  
http://informahealthcare.com/doi/abs/10.3109/13506129.2011.574354083

The introduction of this article gives some background on fibrinogen amyloidosis and refers to the 2009 article by Gillmore, et al (reviewed January 12, 2014) and the 2010 article by Stangou, et al (reviewed February 21, 2014). It then states that this article reports on a systematic study of 25 Portuguese patients with AFib who were followed for a median time of eight years.

The Methods section of the article states that 12 of these patients were identified in a biopsy study, and 13 were identified in a screening study after that. The screening study involved 190 patients from the same geographical area (Braga district of northern Portugal) who were either relatives of the initial 12 patients, or had some reason to suspect amyloidosis, such as kidney failure or proteinuria.

The Results section of the article states that they identified 25 patients with AFib, 14 asymptomatic carriers, and 8 carriers with hypertension. That is a total of 47 patients with the Glu526Val mutation, including the one patient who was homozygous (reported in the 2005 abstract.) The kidney biopsies all showed massive glomerular deposits, but there were some deposits elsewhere. Amyloid deposits were also found in the abdominal subcutaneous fat of one patient. (Fat pad biopsies on AFib patients are usually negative.) Another unusual finding was a family history of renal disease in 80% of the patients, which is much higher than in previously published reports.

The median age at presentation for these patients was 62 years, and the median time from presentation to dialysis was 50 months. Clinically significant medical issues other than renal disease included:
  • Eight patients had strokes.
  • Two patients had severe coronary disease.
  • One patient had echocardiogram findings consistent with cardiac amyloid.
  • One patient had a pacemaker.
  • One patient had resections of the small intestine and the colon. Biopsies of both of the removed sections showed amyloid deposits.
  • Seven patients had peptic ulcer disease.
  • One patient had a spontaneous spleen rupture. Amyloid deposits were found in the ruptured spleen.
  • Four patients had peripheral neuropathy

Only one of these patients had an organ transplant, and that was the patient who was homozygous for the mutation. She had a kidney transplant in 1996, and fourteen years later there was still no clinical evidence of amyloid recurring.

Of the 25 AFib patients, 17 had died as of when this article was written. Their median age at death was 75 years (range 46 to 84), and stroke was the leading cause of death (6 patients).

The article concludes by stating that fibrinogen amyloidosis in this cluster of patients is a systemic disease with high penetrance. It also states that vascular disease was a frequent cause of morbidity and mortality.

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The first thing that stands out about this group of patients is their geographical concentration in one area of Portugal. The Braga district has an area of just over 1000 square miles and a population slightly under one million people. To give you some perspective of how prevalent fibrinogen amyloidosis is in this area compared to the rest of the world, if this same mutation rate of 47 per million people were applied to England and the US, there would be over 2400 AFib cases in England and over 14,000 in the US.

The symptoms beyond kidney disease (extra-renal symptoms) among this group of patients are somewhat similar to the symptoms reported previously in other populations. Even though amyloid deposits are found in other organs, I think it is difficult to determine how much the variant fibrinogen contributed to those other symptoms, and it is almost certainly impossible to predict what organs may be affected in a newly diagnosed patient or one who is just beginning to develop symptoms. The important thing to learn from these various reports of extra-renal symptoms is that fibrinogen amyloidosis is clearly a systemic disease, and one or more organs other than the kidneys will likely become affected to some extent after reaching end stage renal disease.

It is interesting that only one of these patients has received a kidney transplant, and that occurred in 1996. I did a bit of Googling on transplant rates worldwide, and although Portugal is not in the top group in terms of transplants per million people, it seems to be in the second group (out of five.) In fact, all residents of Portugal are presumed to be organ donors unless they opt out, so there should not be a shortage of donors. There are likely many things that factor into the reason for so few organ transplants for these AFib patients, such as the number of experienced transplant centers in that part of the country, but it is odd when compared to the reports from the US and UK. If any of our Portuguese readers would like to comment, please do so, or send me an email. (Se algum dos nossos leitores portugueses gostaria de comentar, por favor, fazê-lo, ou me envie um e-mail. Obrigado.)

In conclusion, this article informs us about a highly concentrated group of AFib patients with presumably close genetic ties who still have the typical variations in age of onset and extra-renal symptoms. If you combine that data with the variations among individuals within a kindred, then in my opinion this seems to indicate that genetics may play only a small role, or perhaps none at all, in determining how or when a person with the Glu526Val will be affected by the variant fibrinogen. The only thing that is remotely predictable is the progression to kidney failure once symptoms develop, but even that has significant variation.

The next article up for review takes us back to the subject of analyzing kidney biopsies.

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Citation:

(1) Tavares I, Lobato L, Moreira L, et al. Long-term follow-up of patients with hereditary fibrinogen A alpha-chain amyloidosis. Amyloid. 2011;18 Suppl 1:221-222.