Saturday, February 28, 2015

Article Review (2009) - A preemptive combined liver-kidney transplantation in A alpha fibrinogen chain renal amyloidosis

Note: Email subscribers are getting this blog post again because when it was first published, there was apparently some strange formatting embedded in it that made things appear wrong in some email readers and on blogspot. I suspect it was some text I copied over from the Google translation of the document. I have gone back and erased all formatting and reformatted it, and it looks much better on the web site now. Hopefully it looks better in email form this time. Here is the original post, again.

It is time for my second blog post of the month, and the first article review since October. Today's article is from 2009 and was published in a French medical journal. You might expect an article to be in French if it is from a French journal, and you would be correct. Although my knowledge of French does not go much beyond what I learned on a Steve Martin album from the 70s ("It's like those French have a different word for everything!"), a couple of things will help me do a half-decent review of this article. First, the abstract is in French and English. Second, Google Translate lets you upload a document for translation, and it did an OK job. So, here we go . . .

Title: A preemptive combined liver-kidney transplantation in A alpha fibrinogen chain renal amyloidosis (1)

Authors: Jean-Philippe Delabre, Georges-Philippe Pageaux, Alain Le Quellec, Pierre Raynaud, Gilles Grateau, Georges Mourad (various hospitals in France)

Journal: Nephrologie & Therapeutique (Nephrology and Therapeutics) (2009)


The predominant cause of hereditary renal amyloidosis is a mutation of the fibrinogen A alpha-chain (AFib), the most common being the E526V mutation. The evolution towards terminal renal insufficiency is constant and raises the question of renal transplantation and the risk of recurrence. We describe the case of a Portuguese woman with the E526V mutation without any renal or hepatic history in her family which developed a nephrotic syndrome at the age of 35, followed by stage 5 renal insufficiency. Because of the risk of recurrence of amyloidosis on its transplant, we carried out a combined transplantation liver-kidney despite the absence of clinical or biological hepatic abnormalities. Four years later, the result is excellent and there is no sign of the disease on the new organs. This successful experience as well as the five other published cases of combined liver-kidney transplantation in A alpha fibrinogen chain amyloidosis, demonstrates the faisability [sic] and efficacy of this treatment in AFib amyloidosis.

First, a note about the abstract: I have probably discussed this in previous posts, but the E526V mutation is the same thing as the Glu526Val mutation. In this context the letter "E" is the one-letter designation for glutamic acid, whereas "glu" is the three-letter abbreviation. Similarly, "V" is the one-letter designation for valine, whose three-letter abbreviation is "val."

The article starts with a brief discussion of hereditary amyloidosis, then states that fibrinogen amyloidosis accounts for the majority of cases of hereditary renal amyloidosis. Kidney transplantation has been performed in patients with fibrinogen amyloidosis, but there is frequently a recurrence of amyloid in the transplanted kidney. Recently there have been reported cases of patients receiving a combined liver-kidney transplant in fibrinogen amyloidosis patients who have either had some liver impairment or a history of amyloid recurrence in a transplanted kidney. The case described in this article is a patient who underwent a combined liver-kidney transplant although there was no liver impairment or family history of amyloid recurrence in a transplanted kidney.

A woman of Portuguese origin born in 1964 presented in January of 2000 with edema. She had proteinuria, high blood pressure, and elevated creatinine, and was determined to be in stage 3 renal failure. Ultrasounds of her kidneys and liver were normal. She had four sisters, two brothers, two uncles and five aunts, none of whom had any known kidney disease.

A kidney biopsy showed amyloid deposits exclusively in the glomeruli, but it could not be typed with immunofluorescence. AL and AA amyloidosis had been ruled out, so familial amyloidosis was suspected. She tested negative for an ATTR mutation. Her kidney disease progressed to the point where she started hemodialysis in November of 2001.

If I understand the translation correctly, the clinical practice where she was being seen in 2000 was only able to test for ATTR mutations. But in 2002 they were able to test for fibrinogen mutations, and she tested positive for the E526V mutation at that time. She was considered a transplant candidate by then, and they decided to do a combined liver-kidney transplant to avoid recurrence of amyloid in the transplanted kidney since such recurrence had already been reported in the medical literature.

She underwent a combined liver-kidney transplant in February of 2004, with her liver being part of a domino liver transplant. At the time this article was written the patient was doing well four years post-transplant, with normal liver function and no sign of amyloid recurrence.

The discussion section of the article discusses some the history and characteristics of fibrinogen amyloidosis, such as:

  • First described in 1993 
  • Likely to be underdiagnosed 
  • Mode of inheritance is autosomal dominant. 
  • Incomplete penetrance often leads to lack of a family history of kidney disease. 
  • Discovery of the disease is always tied to renal issues. 
  • All cases involve proteinuria, usually progressing to renal insufficiency in two to five years. 
  • Hypertension is present in about half of the cases. 
  • Symptoms other than renal issues are rare, with only a few reported cases of liver failure or splenic rupture. 

There is also a good comprehensive table listing all of the published cases of fibrinogen amyloidosis up to this time, giving the number of cases in each family, ethnicity, mutation, age of onset, extrarenal symptoms, and the type of transplant.

There were a few paragraphs discussing the difficulty of diagnosing fibrinogen amyloidosis, but that did not translate well enough for me to paraphrase it here. Then there was some discussion about the justification and considerations for kidney vs. combined liver-kidney transplantation, and the results of each that have been published to-date.


I find the patient in this article noteworthy for two reasons. First, she is from Portugal, which has a very high concentration of fibrinogen amyloidosis patients as previously discussed in the blog posts from April 12, 2014 and April 19, 2014. Second, she first presented with symptoms at the age of 35, which is definitely toward the younger end of the range for age of onset.

As indicated in the title of this article, an important point discussed with regard to this case is the fact that the combined liver-kidney transplant was preemptive in the sense that there were no issues with her liver that would warrant a liver transplant. (The kidney transplant was not preemptive since she was on dialysis.) The first liver-kidney transplants reported were due to recurrence of amyloid in a previously transplanted kidney, so a preemptive liver-kidney transplant for fibrinogen amyloidosis was relatively new. It just so happens that in an article published two months before this one (the study of 71 patients published by Gillmore, et al, reviewed in the January 12, 2014 blog post), three of the seven patients receiving liver-kidney transplants received them preemptively.

The discussion of combined liver-kidney transplantation in this 2009 article, combined with the mention of three preemptive liver-kidney transplants in the study of 71 patients published in 2009, shows how the treatment for fibrinogen amyloidosis was evolving in the mid-2000s. Isolated kidney transplants were the first method of treatment, but then with recurrence of amyloid in the transplanted kidney, combined with the knowledge that the liver is the sole source of the mutant fibrinogen, it made sense to try combined liver-kidney transplants in certain patients. That is definitely a much riskier operation than a kidney transplant alone, so there is a lot to consider when deciding between those two options.

The third transplant option for fibrinogen amyloidosis is an isolated liver transplant, with the recipient from the only known case doing well over four years post-transplant. There is some debate in the medical community regarding that option, but there is certainly no data from that first case to eliminate it as a viable option for healthy patients who are early in the course of the disease. It will be interesting to see how these transplant options evolve over the next several years, and whether or not any drug treatments are successful enough to reduce the need for organ transplants.



(1) J.-P. Delabre, G.-P. Pageaux, A. Le Quellec, P. Raynaud, G. Grateau, and G. Mourad, "Transplantation préemptive foie-rein pour une amylose rénale à fibrinogène Aα," Néphrologie & Thérapeutique, vol. 5, pp. 139-143, 4// 2009.


Edit 4-17-15: Added citation.

Friday, February 13, 2015

Heart Sleep

Today's post will be mostly an update on Mom, covering what has happened since her hospitalization on Christmas Eve due to an increased heart rate (palpitations). I went with Mom to her cardiologist appointment with Dr. R on January 6, and he said the test results from the December hospitalization looked fine. After asking her how often these episodes occur, what are the symptoms, how long do they last, etc., he said he wanted her to wear a heart monitor for a few weeks to hopefully capture an episode so he can see what is going on. His nurse came in after that and described the process for receiving and using the heart monitor. It seems simple enough to use. (It's the SAVI Wireless by Medicomp if you are curious to learn more.) The electrodes she attaches to her chest are wired to a small pendant, and that is all that must stay "attached" to her. The pendant communicates to a cell phone that is part of the system, and the cell phone calls the data in to the central server where all the data is kept. Mom received the monitor in the mail two days after the appointment, and then a day or two after that she got it connected.

An interesting thing came up during the conversation with the nurse regarding the heart monitor, and that was the fact that Mom has not been using her CPAP machine since she had a sinus infection several months ago. Mom's CPAP machine has been a sore subject for several years. It's very big and heavy compared to current styles. Medicaid used to replace them every five years, but that stopped at some point and now I guess they only replace them if they break. Mom's machine is probably closer to 10 years old than it is to 5, and it works fine but is a real hassle to travel with due to the size and weight. Anyway, Dr. R's nurse was familiar with CPAP machines and sleep studies, so she referred Mom to a sleep medicine doctor.

On January 8, Mom saw the sleep medicine doctor (sleepologist?). He suggested she have a sleep study because it had been so long since her previous one, and also because she has lost so much weight since her initial diagnosis of sleep apnea. She had the sleep study the evening of January 13. Unfortunately they told her the following week that she had to do another sleep study for some reason, so she had another sleep study on January 20.

January 29 was a busy day for us because I took Mom to get her new sleep machine in the morning and then we met with her cardiologist in the afternoon. Her new sleep machine is considerably lighter than the old one and has some newer features on it. She was very happy with it and it is doing mostly ok, although there may still be an issue with the mask staying snug all night long.

At the cardiologist appointment Dr. R said the heart monitor did capture a few episodes of increased heart rate, which Mom knew about because she noted them in her book where she records her blood pressure and pulse readings a few times each day. He said it got as high as 150 bpm, which is not good although it is not life-threatening. He said her heart is not having any atrial fibrillation (fluttering heart beat), and he would like to treat it with drugs first. He wants to replace one of her blood pressure medications (Nifedipine) with Verapamil and see how that does. The interesting thing about that is Mom was on Verapamil until November of 2013, when her blood pressure was becoming more difficult to control. The Verapamil was replaced with a different medication when the nephrologist was making some changes to help control her blood pressure. And the reason she was prescribed Verapamil initially several years ago was to control heart palpitations. So hopefully this change to Verapamil will take care of the heart palpitations again.

On his way out the door Dr. R told us the medical term for what is going on with Mom's heart. I did not quite understand the full phrase and it was not something I had heard before, but I did catch the ending which was "tachycardia." So after I got home I asked Dr. Google about it, and based on what I recall Dr. R saying about what is actually happening, I'm 99% sure he said this condition is supraventricular tachycardia. (That's 11 syllables, more than twice as many as "amyloidosis.") A quick read of the Wikipedia article tells me it is rarely a serious condition, and the treatments vary depending on the type of supraventricular tachycardia. So right now it does not seem like it's something to worry too much about.

In other Mom news, her hemoglobin has been having some ups and downs this past month. On January 14, her hemoglobin was up to 12.8 so they stopped given her Epogen during dialysis. Unfortunately it was back down to 10.1 two weeks later, and most recently back up to 11. It is not considered "low" unless it goes below 10, so there is nothing to really worry about yet. We are a couple of weeks past the due date for another trip to the hospital for another GI bleed, so we're keeping our fingers crossed.

In other family news, I had my annual physical last week. Still no signs of kidney problems, so that's good news.

In other other news, someone I went to college with had been posting on Facebook about her mother being in the hospital for several days. She decided to start a CaringBridge page to keep friends and family updated instead of putting all of that on Facebook. I was reading the first entry where she was describing when her mother first became ill and what the symptoms were, and then what was going on with this most recent hospital stay and how the doctors could not determine what the problem was. Then my jaw dropped when I read that she had finally been diagnosed with AL amyloidosis. Small world, eh? I sent her an email telling her about me and Mom, and included some links to the best places to get info online. Hopefully her mother can start healing now that she finally has a diagnosis.

That's all for now. Hopefully I'll get an article review published by the end of the month.

=====Monthly Blog Status Update===== 

As of January 31, 2015:

Total posts: 147 (2 in January)

Total pageviews: 23,000 (~600 in January)

Email subscribers: 12 (unchanged)

Total number of countries that have viewed the blog: 101

No new countries viewed the blog in December.