Sunday, January 19, 2014

Article Review (2009) - Fibrinogen Amyloidosis: A Report of 15 French Cases

Before starting today's article review I want to give a quick update on Mom since it has been almost two months since the last one. There really has not been much going on, which is actually good news. Her calcium level is hovering just below 10, which is high but still within the normal range. No new tests have been ordered, so it seems like trying to figure out the cause of her high calcium is on hold for now. She did recently change her normal dialysis appointment times from 11:00 AM (second shift) to around 6:30 AM (first shift.) That should be more convenient for her to get dialysis taken care of in the morning instead of in the middle of the day. It is early, but if she is tired then maybe she can get some sleep during dialysis.

There is another change regarding dialysis. Mom has requested to be assigned to a different nephrologist. Dr. N has not has not really been bad, but there are some things that Mom has not been pleased with so she inquired about switching a few weeks ago and was told she could do it. So we will see what the new nephrologist thinks about her blood pressure situation.

Today's article being reviewed is an abstract presented at the 2009 World Congress of Nephrology, which was held in May of 2009 in Milan, Italy. As far as I know it is not published in a book and is only available online. This is a short abstract with a correspondingly short review, in contrast to the previous one.

Authors: Laurence Vrigneaud, Jean-Philippe Delabre, Sophie Valleix, Gilles Grateau, Georges Mourad, Philippe Vanhille. (Hospital, Valenciennes, France; University Hospital, Montpellier, France; University Hospital, Paris, France)

Here is the link to this abstract online if you would like to follow along:

As stated in the title, this abstract presents some data on 15 fibrinogen amyloidosis patients from France. I will present most of it in bullet form.

  • 8 women, 7 men
  • 7 patients had the Glu526Val mutation.
  • 6 patients had the Arg554Leu mutation.
  • 2 patients had the frameshift mutation caused by a deletion at codon 522. (Described in the 1997 article reviewed in the April 18, 2013 blog post.)

  • Mean (average) age at presentation was 48.2 years.
  • Average proteinuria was 5.8 grams per day.
  • 8 patients had high blood pressure.
  • 5 patients had microhematuria (blood in the urine).
  • 11 patients had kidney biopsies, which all showed "striking massive amyloid deposits within enlarged glomeruli."
  • 3 biopsies showed amyloid deposits in blood vessels or interstitium (between the cells).

  • 6 patients had no family history of renal disease.
  • The only patient who developed significant clinical symptoms beyond kidney disease was the one with cardiac amyloid. (That case was recently discussed in the January 6, 2014 blog post.)
  • 10 patients were on dialysis within five years of presenting.
  • 3 patients died.

  • 12 patients received kidney transplants.
  • 5 of those patients showed amyloid deposits in the transplanted kidney 4.5 years after transplant.
  • 3 patients received combined liver-kidney transplants, with no recurrence of amyloid two years after transplant.

It is interesting that only 7 out of these 15 patients (47%) had the Glu526Val mutation, since the Glu526Val mutation is the most common. In the previous article that studied 71 patients, 90% had the Glu526Val mutation. But given the small total number of patients in this group from France, one or two families with several members having the Arg554Leu mutation would be a significant percentage of the total. So I don't think we can draw any conclusions based on these numbers.

Among these patients, the typical symptoms we have seen before are proteinuria and high blood pressure. Microhematuria has been mentioned just a few times in earlier articles, so five out of 15 patients having it in this group is a bit unusual. The biopsy results are typical of fibrinogen amyloidosis, since they all showed deposits in the glomeruli and a few showed amyloid deposits elsewhere.

The data on patients who received organ transplants is in line with what we have seen in previous articles. Once again we see that a kidney transplanted without a liver can be expected to have a recurrence of amyloid, whereas a combined liver-kidney transplant seems to prevent recurrence of amyloid.

The concluding paragraph of this abstract ends with this sentence: "DNA analysis is therefore mandatory, regardless of family history, in all patients with renal amyloidosis with selective glomerular involvement, in whom AA or AL fibril type cannot be definitively confirmed." In other words, the authors recommend that in cases where a kidney biopsy shows amyloid deposits primarily in the glomeruli, and AA or AL amyloidosis cannot be confirmed, DNA analysis should be done to look for fibrinogen mutations. That makes sense based on the biopsy findings that have been reported in all the cases up to this point. There are always deposits in the glomeruli, with occasional deposits elsewhere to a lesser extent. The amyloid often cannot be typed, even with immunohistochemistry. We don't need to look any further than Mom's biopsy report to see an example of this. The diagnosis was amyloidosis, with this comment: "There is Lambda greater than Kappa staining but not significant enough to definitively state that this is AL Amyloidosis. The section stained for AA Amyloid is negative." Hindsight is always 20/20, right?

Speaking of biopsy reports, someone on the Yahoo support group recently posted a kidney biopsy report and asked if anyone could translate it. I immediately noticed how similar it was to Mom's biopsy report and offered some of my interpretation. (Bottom line is that the biopsy needs to be sent to Mayo Clinic for analysis by mass spectrometry so the amyloid can be typed.) I did not mention fibrinogen amyloidosis since I would not want to send someone down that path prematurely, but it will not surprise me at all if that is the diagnosis.

Speaking of biopsy reports again, the next article to be reviewed presents another case where the biopsy played a key role in the diagnosis of fibrinogen amyloidosis. Since one of the two authors is the pathologist on the panel at the familial amyloidosis support group meetings every two years, we can expect to get into some detail regarding biopsies.

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