AA Amyloidosis: A Diagnostic and Therapeutic Challenge

ASN Renal Week, Official Symposium, October, 2004

Panel Discussion

Panel Discussion

Dr. Maria M. Picken
Dr. Joseph Mikhael
Question index:
Questions received during this symposium have been paraphrased
and the answers submitted by the panelists are presented.


The presented case surely had glomerular range proteinuria and a glomerular disease. Subsequently it turned out to be amyloidosis. Why, on electron microscopy, did you miss the fibrillary material in the glomerulus?
The third bowel biopsy showed thickening. Did you do a Congo Red stain later on?
Since SAA is elevated, is there any place for plasmapheresis or plasma-absorption therapy?
In presented case, could you have abandoned renal biopsy if you had diagnosed AA amyloidosis earlier on biopsy of colonic mucosa?
Is there any definitive beneficial role of ACE inhibitors or ARBs in amyloidosis? Any role of colchicine, especially in familial Mediterranean fever?
In the presented case, was an SPEP (serum protein electrophoresis) or UPEP (urine protein elecropheresis) ever done?
Dr. Mikhael and Dr. Picken, I enjoyed your talk. My name is Murali. I am from the Mayo Clinic. We are a major referral center for amyloidosis. I would like to bring to your attention the fact that one of the things that is critically relevant to nephrologists is that polyarteritis nodosa or any other necrotizing vasculitis could be a mimicker for amyloid, and if they are interested they could refer to this month's edition of Arteritis/Rheumatism where we have our publication. In your lady if you had done an MRA, you would have seen the characteristic pattern, which we have seen in 3 of our patients. It is a mimicker of collagenous colitis, has the classic beading appearance in the vascular structure, and is very typical of AA amyloidosis.
Do you think that the lipid-lowering therapy that acts also as antiinflammatory and also can lower the HDL can be useful?

Panelist Responses
(Back to question index) The presented case patient surely had glomerular range proteinuria and a glomerular disease. Subsequently it turned out to be amyloidosis. Why, on electron microscopy, did you miss the fibrillary material in the glomerulus?

Dr. Picken: Do you remember when I was showing the pictures that presented the pathology from the autopsy of the liver? The amyloid was very unevenly distributed. Her kidney biopsy was done at an early stage and this single glomerulus simply did not have deposits of amyloid. Keep this in mind. We do not want to make a diagnosis of amyloidosis when you have huge deposits which are immediately apparent at the light microscopic level. You have to think about it and look for it, and you may not find it in a single slide. If you had an opportunity to look at the Congo Red stain slide from an early biopsy, you may see that the deposits are very unevenly distributed. That is an excellent question and I thank you for it.

(Back to question index) The third bowel biopsy showed thickening. Did you do a Congo Red stain later on?

Dr. Picken: Afterwards yes, and it was positive. It is well described in the literature that collagenous colitis is the most frequently rendered diagnosis in patients with AA GI amyloidosis, because people think, ‘Oh, it looks like collagenous colitis, the patient has GI symptoms, it fits.’ It is not the entire story, so beware of collagenous colitis.

(Back to question index) Since SAA is elevated, is there any place for plasmapheresis or plasma-absorption therapy?

Dr. Picken: It is an interesting point, but to my knowledge it has not been tried, and it is probably not very practical. I think that the approach which Joe described, control of SAA release, would make more sense long term, but it is an interesting approach.

(Back to question index) In the case that was presented, could you have abandoned renal biopsy if you had diagnosed AA amyloidosis earlier on biopsy of colonic mucosa?

Dr. Picken: Yes, absolutely, that is the point which I was making. Actually, I am a renal pathologist and you are renal people, but one of the points which we were trying to make is that you do not always need a kidney biopsy in order to diagnose a condition that causes renal symptoms. In this patient, if fine-needle aspiration biopsy was done earlier on, the chances are that amyloid would have been detected. You can also do amyloid typing also on smears, on fat smears, on aspirates, on bone marrow smears, then subsequently later on, on GI biopsies. If somebody thought about amyloid, you already have a diagnosis, You then do the typing, it is AA amyloid. In this particular patient that is probably what is driving the proteinuria. This is an excellent point.

Dr. Mikhael: When I made the comment of looking at the extent of one's organ involvement, it does not mean that every subsequent organ has to be biopsied. We sometimes will go on to biopsy other organs if we want to exclude something else. I had a patient with amyloid in whom we were not sure that the proteinuria was related to the amyloid for a variety of clinical reasons. We pursued it in that light and ultimately did demonstrate the presence of amyloid. It is not like every single organ that is suspected. We would not necessarily recommend that, for example, on our patient that she would have had a biopsy of her thyroid, of her salivary gland, of her colon, of her liver, and of her heart. Those things might guide the initial biopsy, but once the initial biopsy is done, I agree we do not need to repeat them in all of the other organs. Clinically, the diagnosis can be made that way.

Dr. Picken: In particular, the more accessible tissues, abdominal fat aspirate, skin biopsy, fine-needle aspiration biopsy, these are currently available, and they are much more easily performed and obtained, and the same workup can be done.


(Back to question index) Is there any definitive beneficial role of ACE inhibitors or ARBs in amyloidosis? Any role of colchicine, especially in familial Mediterranean fever?

Dr. Mikhael: The ACE inhibitor question, there is no definitive simple answer. I think in the end it is a clinical judgment based on the extent of someone's renal involvement and their overall clinical picture. There has not been a randomized double-blind controlled trial to compare ACE versus no ACE. Obviously, in this context I would say the jury is probably still out, an individual-tailored decision has to be made in each individual case. Colchicine in the context of familial Mediterranean fever has indeed demonstrated benefit and is still used in that context. When attempted in the other context, when the patients have had AA amyloid from other causes, it has not demonstrated significant benefit or potential toxicity, so really it is retained for patients with FMF.

Dr. Picken: This obviously may change if newer and better therapies become available.


(Back to question index) In this patient was an SPEP (serum protein electrophoresis) or UPEP (urine protein electrophoresis) ever done?

Dr. Picken: We did not discuss it, but definitely this is something that should be included, and you would expect it to be negative. We did not have time to discuss the issues of mixed deposits. Clinically, at her age, given her relatively young age, this would not be at the top of my differential, but, yes, one of the very important parts of the workup of a patient with amyloid is clinical pathologic correlation. It has been shown that, yes, some patients may have more than one type of amyloid. We did not want to complicate this case any further, but you would like to make sure that you are not overlooking other conditions, which are treatable; and UPEP and SPEP would be something to do definitely.

(Back to question index) Dr. Mikhael and Dr. Picken, I enjoyed your talk. My name is Murali. I am from the Mayo Clinic. We are a major referral center for amyloidosis. I would like to bring to your attention the fact that one of the things that is critically relevant to nephrologists is that polyarteritis nodosa or any other necrotizing vasculitis could be a mimicker for amyloid, and if they are interested they could refer to this month's edition of Arthritis and Rheumatism where we have our publication. In your lady if you had done an MRA, you would have seen the characteristic pattern, which we have seen in 3 of our patients. It is a mimicker of collagenous colitis, has the classic beading appearance in the vascular structure, and is very typical of AA amyloidosis.

Dr. Picken: It only shows that the list of conditions which could be associated with AA amyloidosis is really much more extensive, and whatever we presented here is not meant to be all inclusive. Thank you very much.

(Back to question index) Do you think that the lipid-lowering therapy that acts also as antiinflammatory and also can lower the HDL can be useful?

Dr. Picken: Well, this is a very interesting question. There has been a lot of interest in the association between lipid metabolism and amyloidosis, in particular, in AA amyloidosis, where there is clearly interplay between HDL, SAA, etc. There have been some studies done, but this would be sort of a secondary effect because you are not attacking the core of the process directly. We think that anti-fibrillogenic compounds, such as Fibrillex may have a better chance, probably by targeting more directly, but it is a bit like the issue of plasmapheresis - this could be perhaps an alternative approach. Now that you have mentioned the issue of the use of statins in the prevention, or at least delay, of different types of amyloid (and it is not only AA, but Alzheimer's disease also has been explored), there is some data to this effect. Antiinflammatory agents for AA, that is sort of an obvious type of approach, but also antiinflammatory treatment in patients, for example with Alzheimer's disease, has also been tried with some modest effect. Definitely, the picture is quite complex and there are also different approaches possible. Thank you for your comment.

Dr. Mikhael: Although the lipid-lowering agents in and of themselves have not demonstrated significant change in the course of one's illness, a simple but I think yet important point – I think we mentioned it briefly in the talk - is to be very aggressive in treating AA patients who have elevated lipid levels because obviously their organ dysfunction is advanced, whether it be cardiac or other, and controlling their lipid levels would be significant.



BACK TO
TOPIC INDEX :