Saturday, March 22, 2014

Article Review (2010) - Recurrence of Amyloidosis in a Kidney Transplant

Today's article being reviewed is another kidney biopsy teaching case from the American Journal of Kidney Diseases. (I reviewed an earlier teaching case in the February 14, 2014 blog post.) In keeping with our recent discussion of organ transplants, this article describes a case in which a transplanted kidney was affected by amyloidosis. It closes with an overview of the published data regarding transplant outcomes for fibrinogen amyloidosis, and includes a suggestion that I find a little strange.

Title: Recurrrence of Amyloidosis in a Kidney Transplant (1)

Authors: Sanjeev Sethi, Fernando Fervenza, Dylan Miller, Suzanne Norby, Nelson Leung (Mayo Clinic, Rochester, MN, USA)

Journal: American Journal of Kidney Diseases (2010)

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

This article starts by mentioning there are many reasons kidney transplants fail over time, with rejection, hypertension and infection being some of the more common causes. It then states that the cause of transplant dysfunction in this case was identified on a biopsy.

This case is somewhat interesting because it includes a misdiagnosis of AL amyloidosis. Around 1990, a 50-year-old man developed hypertension and type 2 diabetes. At the age of 58 he was found to have proteinuria, and a kidney biopsy showed amyloidosis. Stem cells were collected in anticipation of a stem cell transplant, but the stem cell transplant did not proceed because his kidney failure progressed to the point where he required dialysis.

In May of 2000, at the age of 60, this patient was evaluated at the Mayo Clinic for a second opinion regarding his advanced kidney disease and treatment for amyloidosis. A bone marrow biopsy and fat pad biopsy were negative for amyloidosis, and a cardiac echocardiogram showed no evidence of amyloid. Since there was no evidence of a plasma cell dyscrasia (abnormality) to indicate AL amyloidosis, familial amyloidosis was suspected. Genetic testing showed he had a mutation for fibrinogen amyloidosis.

The patient received a kidney transplant from a living donor in August of 2003. There were some minor complications discussed in the article, but it was successful. After things stabilized his serum creatinine was 1.7 mg/dL, and his measured GFR was 61. (Side note: Normally we see estimated GFR, sometimes written as "eGFR." But there are methods to actually measure the GFR based on how quickly something is filtered out of the blood or into the urine.) The article then gives the results of his annual evaluations for the next several years (skipping 2006). Kidney biopsies were done most years as a matter of protocol.

2004: Biopsy showed no sign of rejection.

2005: Creatinine=1.7; GFR=53; Proteinuria = 59 mg/day. Biopsy showed "a mild increase in interstitial fibrosis."

2007: Creatinine=1.8; GFR=43. Congo Red staining of the kidney biopsy was negative, but some amyloid fibrils were visible under electron microscopy. This was the first indication that amyloidosis was recurring. Mass spectrometry showed the amyloid deposits were composed primarily of variant fibrinogen.

2008: Creatinine=2.0; GFR=40; Proteinuria=86 mg/day. Biopsy showed amyloidosis on light, immunofluorescence, and electron microscopy.

2009: As of July of 2009, nearly six years post-transplant, measurements of kidney function were essentially the same as they were in 2008.

The articles then goes into some more detail on the findings of the all of the kidney biopsies, both pre- and post-transplant. The Discussion section of the article gives a basic overview of how amyloidosis is diagnosed and typed, then it gives a summary of this particular case. There was a significant decrease in kidney function four years after transplant although Congo Red staining was negative at four years and positive at five years post-transplant.

After a quick overview of fibrinogen amyloidosis, the kidney transplant results from the 2009 article by Gillmore, et al (reviewed January 12, 2014) are discussed. That article reported on 12 kidney transplants, with three failing due to technical difficulties (not amyloidosis related) and amyloidosis recurring in four of the remaining nine. One of those kidney transplants in which amyloidosis has recurred was still functional after 12 years.

The use of combined liver-kidney transplants (LKT) is then discussed, with the article mentioning that LKT has been successful in preventing recurrence of amyloidosis because removing the liver removes the source of the variant fibrinogen. Near the end of the article is a sentence that includes a suggestion regarding organ transplantation that I do not recall seeing before: "Because recurrent fibrinogen A alpha-chain amyloidosis is slow to develop, it has been suggested that liver transplant be performed only after recurrence results in transplant failure." That would certainly not be my suggestion, but I can see how someone could make a case for that. In my opinion, if you think you might need a liver transplant after a kidney transplant fails, and you think you will be healthy enough for it, then you might as well get a combined liver and kidney transplant now.


Although we have seen several articles mention recurrence of amyloidosis in kidney transplants, this article is the first one to provide the details of the clinical history of such a recurrence. Keep in mind that the time from transplant to amyloid recurrence to transplant failure varies over a wide range, and this case is just one sample from that group. A few important items to note from this article are:

  • The progression of kidney failure when amyloid recurs is slow, much like it is was when the native kidneys were first affected by amyloid.
  • As a result of this slow progression, recurrence of amyloid in a kidney transplant does not indicate an imminent failure of the transplanted kidney. (I think it would be fair to say a recurrence of amyloid does indicate an eventual failure of the transplanted kidney.)

The topic of transplant options was also discussed in this article, including a suggestion that seems a little strange at first glance. (Do not get a liver transplant until after your first kidney transplant fails.) There are typically no easy answers regarding organ transplants to treat fibrinogen amyloidosis, and we have seen that there is not a consensus of opinion in the medical community. Since we seem to be discussing transplants a lot lately, and our knowledge base is expanding quite rapidly as we include more and more published data, I am in the early stages of developing another standalone page to present the pros and cons of the various transplant options. So that page may magically appear in the next month or two.



(1) Sethi S, Fervenza FC, Miller D, Norby S, Leung N. Recurrence of Amyloidosis in a Kidney Transplant. Am J Kidney Dis 2010; 56: 394-398.

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