Before getting to the article review I need to mention that some of my writing about amyloidosis has been published elsewhere. In case you have not already seen it, I wrote an article for the Spring 2015 edition of the newsletter published by the Amyloidosis Foundation. (http://www.amyloidosis.org/)
The newsletter can be found on the Publications page of the Amyloidosis Foundation web site: http://www.amyloidosis.org/AboutAmyloidosis/publications.html
If that link does not work for you, here is the direct link to the PDF file: http://www.amyloidosis.org/pdf/Spring_2015_newsletter.pdf
My article starts on page 7. It was challenging to condense two and a half years of blogging into 700 words or less, but I think I did ok.
The subject of the article being reviewed in this post is amyloidosis in kidney biopsies, so it deals primarily with AL and AA amyloidosis. Fibrinogen amyloidosis is mentioned, and there is an interesting graph that presents some data in a way that supports something we have seen in other articles.
Title: Prevalence and Origin of Amyloid in Kidney Biopsies (1)
Authors: Hanna von Hutten, Michael Mihatsch, Hartmut Lobeck, Birgit Rudolph, Magdalena Eriksson, and Christoph Rocken (Charite University Hospital, Berlin; Ernst von Bergmann Hospital, Potsdam, Germany; Universitatsspital Basel, Switzerland)
Journal: The American Journal of Surgical Pathology (2009)
We aimed to reassess renal amyloidosis in kidney biopsies with a focus on possibly misclassified or unclassified cases and changes in the prevalence of different amyloid types. Two hundred thirty-three kidney biopsies obtained from 231 patients diagnosed with amyloid during the period from 1990 to 2007 years were included in this retrospective study. Amyloid was identified by Congo red staining and polarization microscopy. Immunohistochemical classification was made with antibodies directed against AA amyloid, apolipoprotein A1, fibrinogen, lysozyme, lambda-light chain, kappa-light chain, beta2-microglobulin, transthyretin, and amyloid P-component. Amyloid was present in each biopsy as vascular, tubulo-interstitial and/or glomerular deposits. Immunoglobulin light chain-derived (AL) amyloidosis was most prevalent and diagnosed in 123 (53.2%) patients. It was categorized into AL amyloid of lambda-light chain (AL lambda) [105 (85.4%) patients] and kappa-light chain origin (AL kappa) [10 (8.1%)]. The amyloid deposits of 8 (6.5%) patients were not clearly distinguishable into AL lambda amyloid or AL kappa amyloid and categorized as AL amyloid, not otherwise specified. Reactive systemic amyloid A (AA) amyloidosis was the second most common type and was found in 93 patients (40.3%). Overall 7 patients were found to suffer from fibrinogen A alpha-chain-[amyloid of fibrinogen (AFib); 4 (1.7%) patients], transthyretin-[amyloid of transthyretin (ATTR); 2 (0.9%)], or apolipoprotein A1-derived (AApoAI) amyloidosis [1 (0.4%)]. In 8 patients (3.4%) the amyloid deposits remained unclassifiable. After additional immunostaining and further clinical information the diagnoses of 12 patients (5.1%) were modified (2 ALlambda amyloid, 4 ALkappa amyloid, 1 amyloid unclassified, 3 mixed-type amyloidosis, AA+ATTR, AL lambda+ATTR, and AL kappa+ATTR, 1 AFib, and 1 AApoAI). Although the histologic and immunohistochemical reevaluation confirmed the classifications in 221 (95.7%) patients. Renal amyloidosis is most commonly of AL lambda-origin, followed by AA amyloidosis. AFib amyloidosis was found to be the most prevalent type of hereditary renal amyloidosis, illustrating the necessity of a thorough classification of the amyloid proteins.
Here is a link to the article (not freely available) if you would like to follow along: http://www.ncbi.nlm.nih.gov/pubmed/19561448
As you can probably tell from the list of authors and their affiliations, the data from this article comes from Europe. The authors analyzed the data from kidney biopsies submitted to three different pathology departments (two in Germany and one in Switzerland) between 1990 and 2007. These biopsies were then reassessed for the presence of amyloid and typed using immunohistochemistry (staining). Here is a quick summary of the numbers:
- 13,921 kidney biopsies were submitted between 1990 and 2007.
- 233 biopsies were diagnosed with amyloidosis (1.7% of the total biopsies).
- Of those 233 biopsies diagnosed with amyloidosis, the type was determined in 225.
- AL and AA amyloidosis were the most common types (54% and 41% respectively).
- Only 7 were typed with hereditary amyloidosis, including 4 (1.7%) with fibrinogen amyloidosis (Glu526Val mutation).
The reassessment of these biopsies did result in the reclassification of a few, including one with fibrinogen amyloidosis that was initially typed as AL amyloidosis. That is not too surprising, especially considering the 2002 article "Misdiagnosis of Hereditary Amyloidosis as AL (Primary) Amyloidosis" (reviewed in the May 12, 2013 blog post) which found 34 out of 350 patients with a hereditary type of amyloidosis had been misdiagnosed with AL amyloidosis.
The article then provides a lot of detail on the findings among the AL and AA patients which I will not cover here. In the discussion of fibrinogen, they mention the unique appearance of those amyloid deposits when compared to deposits due to AL or AA amyloidosis. Other articles on AFib have mentioned the concentration of amyloid deposits in the glomeruli of the kidneys, but this is the first article I recall that has this much to say about it. Below I have quoted the relevant parts of the article, followed by a graph from the article. Keep in mind that these conclusions are based on just four biopsies with fibrinogen amyloidosis, but they do seem to align with other published descriptions of biopsies from AFib patients.
[Reminder: The glomeruli are the small blood vessels in the first stage of the kidney where water and impurities are initially filtered out. Fibrinogen amyloidosis deposits tend to accumulate there.]
The histologic appearance of AFib amyloidosis was unique and common to all 4 patients. Amyloid was found only in the glomeruli with large deposits, showing a smooth and even outline.
All patients with renal AFib amyloidosis were characterized by a unique and pathognomonic glomerular manifestation without any extra-glomerular renal amyloid deposits. The glomeruli were evenly enlarged, sometimes reminiscent of cotton balls, with soft contours of the loops. Due to its unique histologic appearance we were finally able to suspect AFib amyloidosis already on conventional hematoxylin and eosin stained sections.
As described in previous studies, we noticed that the different types of amyloid present with slightly variable amyloid deposition patterns. Only the deposition pattern of AFib amyloidosis was unique among all types of amyloid.
What they are essentially saying is with fibrinogen amyloidosis, the amyloid deposits in the kidney are exclusively in the glomeruli, unlike other types of amyloidosis (AL and AA) where the amyloid deposits are found not only in the glomeruli but elsewhere. This information is presented graphically in Figure 2 from the article, shown here:
The different colored bars in this graph each represent a different description of the location of amyloid deposits on the biopsy slides. The three categories are Glomerular, Glomerular-Vascular (in the glomeruli as well as other blood vessels), and All. The "All" category means the deposits were found not only in the glomeruli and other blood vessels, but there are also tubulo-interstitial deposits, meaning within and between the tubules (another structure within the kidney.) In the graph above we can see for AL and AA amyloidosis there were some biopsies in each of the three categories, whereas the biopsies of the AFib patients were all categorized as glomerular only (the darkest of the three bars.)
As I mentioned earlier it is important to remember that this is a very small population of four biopsies. But if we were to go back and read all of the published renal biopsy descriptions of AFib patients, I am sure we would notice the majority of them mention a heavy or exclusive concentration of amyloid deposits in the glomeruli. That does not mean AFib can be positively diagnosed based solely on the appearance of the amyloid deposits, but it is a reason to suspect AFib. Correctly typing from a biopsy slide requires more advanced methods such as immunohistochemistry and mass spectrometry that have been covered in other articles.
That's about it for the relevant parts of this article. It does show how rare amyloidosis in general is, with amyloid deposits detected in less than two percent of the kidney biopsies of this population. And then as we have seen in other articles, fibrinogen amyloidosis is a rare subset (in this article less than two percent) within that two percent. Although nobody feels lucky to have fibrinogen amyloidosis, those of us with a diagnosis should feel fortunate to at least have the correct diagnosis.
=====Monthly Blog Status Update=====
As of February 28, 2015:
Total posts: 149 (2 in February)
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Email subscribers: 12 (unchanged)
Total number of countries that have viewed the blog: 101
No new countries viewed the blog in February.
Edit 4-1-15: Corrected monthly stats.
Edit 4-17-15: Added citation