Monday, December 28, 2009

When Should The Chance Of An Exceedingly Rare Disease Disqualify A Kidney -- For Donation?

That is the fascinating, and difficult question raised in today's New York Times story on two separate kidney-transplant patients that appear to have contracted a very rare infection, from an individual donor-source. [Strictly speaking, this item strays from the core topic this blog covers, as neither Schering-Plough, nor Merck makes any kidney transplantation instrument, kit, device or anti-rejection drug.]

With the well-documented shortages in available kidneys, the questions include risk-to-benefit assessments, as well as informed consent possibilities. Should a donated kidney be implanted -- once the consenting patient is warned of the potential for a disease -- given that it is not really feasible to screen each donated organ for every remotely-possible potential bacterial or other problem? Do go read it all -- as it is quite thought-provoking.

From The New York Times story -- a snippet, then:

. . . .All the tests were negative, so [this donor's] heart, liver and kidneys were transplanted into four patients. Afterward, an autopsy still missed the infection and seemed to support the mistaken diagnosis.

About three weeks after the transplants, both kidney recipients became severely ill, within hours of each other, with seizures, fever and changes in their mental status. They were taken back to the hospital in Jackson. A doctor there noted that both had had kidney transplants the same day. He suspected immediately that the kidneys had come from the same donor and that the donor might have had an undetected infection.

The hospital sent samples of the donor’s brain tissue to the disease centers, which found an amoeba called Balamuthia mandrillaris. One kidney patient was then given a biopsy, which also tested positive for the amoebas. Balamuthia lives in soil and water, and scientists suspect that people become infected through cuts or from ingesting the organism. Only about 70 cases have ever been identified in the United States, and nearly all have been fatal. These are the first known cases from transplants.

It was not clear why only the kidney patients had become ill. The kidneys may have harbored more amoebas than the other organs, Dr. Farnon said, or the particular anti-rejection drugs might have been a factor.

The patients are being treated with “a boatload of drugs,” Dr. Schlessinger said, but have not improved. . . .

I think it likely that the anti-rejection drugs (with their generally salutory by-design immune supression properties -- to decrease chances of organ rejection) were, in part, a cause here. But if the alternative was to die of end stage renal disease, I am perplexed, but leaning toward the notion that this was all a risk worth assuming.

[Note: My image, above right, as re-imagined and heavily-edited from a Canadian educational site on medicine, and kidney transplantation.]

1 comment:

Anonymous said...

I'm with you here. You have to be reasonable about things.

If only 70 people have ever died in the US from this. (Assume 2 cases per year). What is the underlying incidence without death (still likely very low). Of these the chance of being transplanted is even lower.

We might assume that everyone transplanted with a kidney from someone with the infection will die but how do we know that the amoeba generally logs in the kidney and just wasn't high in this case.

Even being extremely cautious we could first try to culture it from every patient with a tranplant who dies from an unknown cause shortly after transplant. We might then have a better chance of determining the true risk.

You have to look at all factors.

For example take a drug trial. you can say only 2 people died from X during development in 2500 patients (typically companies won't even admit both the 2 cases are the same thing). But if you look closer you may find both cases occurred in the patients on the drug for 18 months or longer so the risk rises to 2 deaths out of 20 patients on drug that long. Plus if you look at SAEs in this pop you may find another 4 patients who didn't die but could also have the same underlying toxicity. Plus you may find softer signals for the same toxicity in other patients.

Consequently you now have a potential risk of 1/3 of patients dying or being seriously hurt if on a drug long term.

Ideally there would be simple lab tests that could be used to confirm or refute the toxic mechanisms in a couple of days. In some cases it would be expected that these tests would be done automatically with any drug under development that has a known potential a priori to result in these toxic mechanisms. So if these tests aren't done and the deaths are covered up it should raise suspicions.

I believe in either situation it is best to act prudently.