Thursday, April 30, 2015

Article Review (2007) - New insights into systemic amyloidosis: the importance of diagnosis of specific type

It looks like I have once again waited until the last minute to get a monthly blog post written. Fortunately today's article review will be rather short since this article only briefly mentions fibrinogen amyloidosis. In the interest of completeness I still need to review it, but first, a partial update on Mom.

In the previous update on Mom (February 13, 2015) she had just started using her new CPAP machine and her cardiologist had prescribed a change in her medication to control her heart palpitations. What has happened since then?

On March 12 she had a regularly scheduled appointment with Dr. K to check on her fistula. He said there was some blockage that had gone from moderate to severe, so she needed to have another balloon angioplasty to open up those blockages. This was not an emergency and it is just something that happens over time as a fistula ages and gets used. She had the procedure on March 17 and it went fine.

On Friday, March 20 Mom started having heart palpitations toward the end of dialysis and had to be taken home. Her pulse rate got as high as 155 bpm. Fortunately she did not feel any chest pain this time and she recovered quickly from it. Based on this episode and the one that put her in the hospital on Christmas Eve last year, we think these heart palpitations can be induced at dialysis when they try to remove too much fluid from her, or remove it too fast. So she will have to make sure any dialysis tech that gets her set up is aware of those limitations.

Since Mom is back on the list for a kidney transplant she has to be evaluated annually by the pre-transplant group. She had an appointment on March 25 where they did an echocardiogram and went over her medical records. That was an interesting discussion to say the least, so I will continue that story with the next blog post. Now it is time for a short article review.

Author: Maria Picken (Loyola University Medical Center, Illinois, USA)

Journal: Current Opinion in Nephrology and Hypertension (2007)


Purpose of review: This review aims to summarize recent developments in the area of systemic amyloidoses with emphasis on pathologic diagnosis.
Recent findings: In recent years, management of amyloidosis has shifted from a purely supportive approach to quite diverse, radical and aggressive treatments. The central issue is the understanding that treatment of systemic amyloidoses depends on the molecular type of the amyloid protein. In the United States and the Western world, AL-amyloidosis is the most prevalent type of systemic amyloidosis, but hereditary amyloidoses are being diagnosed with increasing frequency; genetics also plays a role in a subset of familial AA amyloidoses. The biggest challenge is in the diagnosis of AL-type with confidence and in differentiation of AL and hereditary amyloidoses. While careful clinico-pathologic correlation is recommended for all patients with amyloidosis, it is, in itself, not a substitute for amyloid typing.
Summary: The diagnosis of the amyloid type ultimately depends on the examination of the amyloid protein within the deposits. The role of immunohistochemistry – the current standard of care in amyloid typing – is evolving with emergence of alternative biochemical methods. Amyloid, being essentially a protein disorder, presents an attractive venue for the application of proteomics methodologies, despite their inherent complexities.

Here is a link to the article (not freely available) if you would like to follow along:

The author of this article, Maria Picken, is a well-known pathologist in the amyloidosis community. We have seen her name at least twice in previous article reviews, and she has also been on the panel at the familial amyloidosis support meetings that are held every two years in Chicago. You might say she literally wrote the book on pathology as it relates to amyloidosis, because she was not only one of the editors of the book Amyloid and Related Disorders, she also wrote five of the 33 chapters in the book.

This article from 2007 gives a broad overview of the different types of amyloidosis and the importance of properly typing the amyloidosis before deciding on a treatment. I will not go over that since it has been discussed in previous articles. Regarding methods of typing by analyzing biopsy tissue, mass spectrometry was very new at the time this article was published, so the article focuses primarily on immunohistochemistry, which is staining for specific proteins. Again, I will not go over that here because it has been covered in previous articles.

What I will discuss here is a couple of paragraphs that specifically relate to fibrinogen amyloidosis. Here is the first one, in the section of the article that gives an overview of the various types of familial amyloidosis.

Amyloid derived from the fibrinogen A alpha chain (AFib) appears to be the most common form of hereditary amyloidosis in the UK and northern Europe. Amyloid deposits in AFib are quite unique in that they appear to selectively target glomeruli and lead to their complete obliteration, with sparing of the extraglomerular compartments. Renal failure rapidly develops.

We have seen similar descriptions of fibrinogen amyloidosis deposits in other articles (such as the article from the previous article review), but hearing it from a pathologist with as much experience as Dr. Picken does give some weight to the statement.

In the section of the article on treatment of systemic amyloidosis there is a discussion of liver transplantation for patients with transthyretin amyloidosis (ATTR). Due to the risks associated with liver transplantation, it was initially only offered to patients in whom the disease had progressed. But it has since been recognized that better results can be obtained by performing liver transplantation earlier in the progression of the disease. (We are still talking about ATTR here.) Then there is this bit of information I have not seen before regarding liver transplantation for ATTR:

Interestingly, heavy amyloid deposits in the kidneys, especially in the glomeruli, may portend a poor outcome for liver transplantation. Thus, kidney biopsy has been proposed as an outcome predictor for liver transplantation.

First, the article that reported those outcomes was for liver transplantation in patients with the Val30Met ATTR mutation. It was not for liver transplantation in general. But it does make sense based on what I learned when Mom was denied a liver transplant, because the medicine required post-transplant is very hard on the kidneys. The less kidney function there is remaining before the transplant, the more likely there is to be compromised kidney function after the transplant, leading to complications. This is another reason why it is better to start thinking about organ transplantation as soon as possible. Time is of the essence if you decide to pursue a liver-only transplant.

The article then mentions that hepatorenal transplantation (combined liver-kidney) has been successful in treating patients with fibrinogen, apolipoprotein A1 and apolipoprotein A2.

As I mentioned in the beginning of this review, this article does not give us much new information about fibrinogen amyloidosis. It does serve to further support the statement that fibrinogen amyloidosis deposits tend to concentrate in the glomeruli. Unfortunately, given the rarity of amyloidosis in general, very few pathologists will analyze enough biopsies to be able to make that determination. And even if they do suspect fibrinogen amyloidosis when looking at a biopsy, it still needs to be properly typed with one of the more advanced methods.

The next post will reveal what was learned when Mom discussed her medical records with the pre-transplant group, and what unfolded after that.

=====Monthly Blog Status Update===== 

As of March 31, 2015:

Total posts: 150 (1 in March)

Total pageviews: 24,200 (~600 in March)

Email subscribers: 12 (unchanged)

Total number of countries that have viewed the blog: 101

No new countries viewed the blog in March.


(1) Picken MM. New insights into systemic amyloidosis: the importance of diagnosis of specific type. Curr Opin Nephrol Hypertens. 2007;16(3):196-203.

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