Tag: Transplant

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The best story that wasn’t nominated.

Its oscar season in nephrology. The RFN is winnowing down the top stories in nephrology of 2013 but maybe the most important isn’t even nominated. It came out too late. On November 27, Kidney International released this study in advance of print:

The bullet point I learned in fellowship was that the rate of renal failure in kidney donors was no higher than the general public, of course the kidney donors are screened to be much healthier than the general public, so the fact that the rate of renal failure is not significantly lower than the general public is an important signal.

Have I mentioned how
much I love MedCalc?

Donors don’t have obesity, diabetes, hypertension. Of course most of them also have family history of kidney disease, so when they do develop kidney failure attributing the cause cause can be tricky, certainly some of these people would progress to renal failure even if they didn’t donate.

Into this statistical Gordian knot wades the Norwegians.

  • 15 years of follow up for donors that were 46 years old at the time of donation. That is adequate follow-up in my mind.
  • Their center had no preoperative mortality. They did 2,269 living donations with out losing a donor. Great work by the surgical team.
  • They found an increased risk of death by any cause, HR 2.49 (CI 2.13-2.91). 
  • Adjusted HR for all-cause mortality fell to 1.48 (CI 1.17-1.88). 
  • I used their raw mortality data to calculate the Number Needed to Harm. It was a frightening 23 (4.3% absolute risk increase). I do not think this is a valid use of NNH, see below.
  • The CV Mortality HR was 1.4 (CI 1.03-1.91).
  • ESRD was increased from 0.01% per year to 0.03% a relative risk of 3 but a number needed to harm of 5000. (i.e. you would have to do 5,000 living transplants a year to see one additional cases of dialysis in a donor)
The lines only begin to separate after 10 years. This indicates that we should probably ignore studies with less than a decade of follow-up
The data is eye opening, but I would really be interested in seeing what the difference between first degree relatives and people not related. I think much of the increased danger comes from being related to the patient who needed the transplant in the first place.
I also recommend ignoring all the unadjusted data (including the number needed to harm) because the control group was nearly a decade younger than the donors. A ten year difference in age when the total follow-up is only 16 years makes the unadjusted data deceptive, IMHO.
I would love to see a study where the control group was made up of other people who were evaluated and cleared to donate a kidney but ended up deferring, due to the recipient getting another organ or dying or going off the list for some other reason. That would be the ideal control population.
The reality is that people want to donate a kidney to their loved ones. Telling them there maybe a small increase risk of death when you are in your late 50’s or early sixty’s. Will probably not eliminate many close relatives, but altruistic donors and family members should be aware of the risks as understood today. It is probably time to bury the old line about “No increased risk of renal failure than the general public.”

Another study on this from 2010 can be read here.

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Twitter, kidney transplants and misinformation–Updated

Last week Indiana University (@IU_Health) live-tweeted a kidney transplant. They claimed it was the first unrelated-living-donor transplant Live tweeted.

It was dramatic and there was a lot of buzz among the kidney folk on Twitter about this. You can read some of the coverage here. It was exciting but it tasted too much like a publicity stunt for my taste. The counter argument, of course, is that raising the profile of living unrelated donors increases the likelihood that people will come forth and donate and I should just swallow my distaste and be supportive of the outreach effort.

We need more living donors.
We need more deceased donors.
We need more kidney donors.

As part of the Twitter publicity campaign, IU_health tweeted various facts about transplant. This one seemed wrong to me:

One every twenty minutes
Three an hour
Seventy-two a day
26,280 deaths a year 
That’s a lot
That’s too many
When I first read the tweet I read it as “1 American dies every 20 minutes waiting for a kidney transplant.” Twenty-six thousand deaths out of the ninety-thousand people on the wait list seemed like a very high mortality rate, higher than the dialysis morality rate. A quick check in the USRDS Atlas revealed the mortality rate to be only 7% on the wait list.
When I went back and read the tweet again I saw that they were talking about people waiting for all transplants. This seemed more than a bit disingenuous because when we encourage people to become living donors we are only talking about kidney transplants (in 2008 there were only 250 living partial liver transplants). I assume that IU is not encouraging living donors for hearts and lungs. 
In 2008 there was only 4,638 deaths among people waiting for a kidney transplant. For all organs it was only 7,182 deaths. These numbers are from Health Resources and Services Administration. Similar data can be found in USRDS Atlas Volume 2 Chapter 7 (PDF).
We need more kidney donors and social media is a great tool to unlock the thousands of spare kidneys Americans carry around with them but the great need does not justify spreading lies and misinformation.
Literally minutes after I posted this I received the following tweet:
Kudos for IU Health in coming clean. Also Hat tip to Sunny Gill, one of our first year fellows for finding the HRSA website.
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You hear about the kid who sold his kidney for an iPad?

This tragic story has been flying around the internet for the past few days. The story was broken in the western press by Reuters who described a 17-year old named Wang from Hunan who was paid $3,500 for his kidney which was subsequently sold for $35,000 to a patient in need of a transplant. The story originally surfaced last April (strangely his name at that time was reported as Zheng, but so many of the details line up I’m certain this is the same kid) but now that five people are being prosecuted and poor Wang is suffering from renal insufficiency the story is “hot” again. Apparently Wang will likely need a kidney transplant of his own soon.

The part of the story that irritates me is the implication that donating the kidney is the cause of Wang’s failing kidney. This is implied and to the lay person it makes total sense. God gave you two kidneys. You better not donate one or you could end up needing a transplant yourself.

This is the wrong conclusion. Donating a kidney does not increase your risk of dialysis, transplant or poor quality of life. This is best illustrated in Ibrahim et al’s retrospective study of 3,698 kidney donors from 1963 to 2007.

The study population was the entire cohort of living donors from the University of Minnesota. This population, prior to donating is free of diabetes, hypertension and had a GFR >80 mL/min. Additionally they had no albuminuria. Of course, many of them had a relative with ESRD.

Eleven of the 3,700  (0.3%) donors ultimately needed dialysis or transplantation. The average time from donation to ESRD was 22.5±10.4 years. Seven of the unfortunate, donated to a sibling and only three lost their kidneys due to the same etiology as their recipient.

…estimated incidence of ESRD in donors would appear to be 180 per million persons per year, as compared with the overall adjusted incidence rate of 268 per million persons per year in the white population of the United States.

Idea: to lower the epidemic of ESRD, get everyone to donate a kidney and we can reduce the incidence of ESRD by a third.

The remainder of the article goes through the deep analysis of the 255 donors who were invited for further testing.

  • Creatinine had gone from 0.9 at the time of donation to 1.1 an average of 12 years later
  • GFR went from 84 to 63 mL/min
  • 11.5% developed microalbuminuria
  • 1.2% developed macroalbuminuria

Thirty-eight donors have returned for two iothalamate GFRs at least 3 years apart. The investigators found the average loss of GFR was 0.6 mL/min per year.

One of the reasons that donating a kidney is safe is that the remaining kidney undergoes hypertrophy to accommodate the increased work-load. The investigators were able to provide some insight into the variables which govern this. Increased compensation correlated with:

  • younger age at donation
  • higher renal function at donation
  • longer time since donation

This final graph should be the take away for discussing kidney donation:

Kidney donors report better physical and mental health than the US average.

When I counsel patients on the safety of kidney donation or medical nephrectomy I need to fight the pre-conceived notion that loss of renal function occurs nephron-by-nephron, so that losing half the nephrons through a nephrectomy halves the time to dialysis. People seem to visualize kidney function like a bathtub draining water. High blood pressure and proteinuria open the drain wider so the water drains out faster. Using that visualization, a nephrectomy is like losing half the water and putting you much closer to dialysis.

The image I try to paint is that losing renal function is like melting an ice cube, people start with two ice cubes. When the ice is gone the patient needs a transplant or dialysis. Poorly controlled blood sugars, high blood pressure and proteinuria turn up the ambient temperature so the ice melts faster, but it melts both the left and right cube at the same time.  A nephrectomy removes one of the ice cubes but it does not necessarily reduce the time until all the ice is gone.

The last point that needs to be made about this story is that shady, back-street organ selling scams are designed to line the pockets of the broker and surgeon. They do not have the best interest of the kidney donor in mind. The tragic outcome of young Wang is typical for these third-world, kidney-for-money scams. JAMA published a great article showing the typical experience in India a decade ago. It’s still worth reading.

Thanks to Dr. El-Ghoroury for help with this post. Follow him on Twitter @melgho

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Most depressing statistic in nephrology

The Scientific Registry of Transplant Recipients (SRTR) prepares an Annual Report in collaboration with the Organ Procurement and Transplantation Network (OPTN) on the state transplants in America. In 2008 there were fewer transplants done than in the previous year. Kidney transplants peaked in 2006 at 18,059 and have fallen for two straight years.

The total number of organs transplanted decreased from 27,586 in 2007 to 27,281 in 2008. This was an overall decrease of 305 organs transplanted (1.1 percent), including 91 (1.4 percent) fewer living donor transplants.

Here is the data on kidney transplants displayed graphically. Note the ever increasing demand for transplant as represented by the number of patients on the waiting list:

Here is the same data from the USRDS:

Increasing number of patients on the wait list, longer waiting times and fewer total transplants. Terrible.
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Go green: recycle your organs

On of my patients, whose daughter had a kidney transplant, came into clinic wearing this T-shirt. Love it.
It says. “My child contains recycled parts. Be a hero, be a donor.”
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Post transplant erythrocytosis

I have a 35 year old patient who recently received his second kidney transplant. He received his first transplant in his 20s in Albania after going into renal failure due to SSG (that’s Some Sort of Glomerulonephritis, a typical diagnosis for a patient who emigrates to the US with a failing transplant and little medical history).

Soon after his transplant his hemoglobin began to rise. We initiated phlebotomy when his hemoglobin rose above 19.

His hemoglobin fell to 17.2 but then increasd up to 18.5.

I started 5 mg of enalepril and it fell to 16.9.

I increased the enalepril to 10 mg and it fell to 16.2 and continued to fall until it is now around 14.

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Journal Club: dialysis time, not the critical factor in graft survival

One of the inherent truths in transplant is that the longer someone is on dialysis the worse the outcome after transplant. Patient with higher dialysis vintage prior to transplant are more likely to lose their graft and die following transplant. This was first shown by Cosio Et al. and subsequently verified by other researchers.

Cosio’s primary figure showing dramatically increased mortality with increasing time on dialysis

Though Cosio et al. was the first (?) to find this association the most elegant data comes from Meier-kreiesche, Et al. who looked at graft survival when a paired sets of cadaveric kidneys is donated to recipients with differing duration of dialysis. By looking at paired kidneys they were able to neutralize any confounding factors from the donor. The primary analysis looked at kidneys that were split between one recipient with less than 6-months of dialysis and another with more than 2-years of dialysis. The end-point was graft survival:

They also calculated patient survival and they likewise found a significant splay based on time on dialysis:

Five- and ten-year unadjusted overall patient survival for paired kidneys was 89% and 76%, respectively, in the group on dialysis less than 6 months compared to 76% and 43%, respectively, in the group on dialysis for more than 2 years (P<0.001 each).

The obvious implication was that dialysis was bad for you. The longer you were on dialysis the more baggage you were carrying at the time of transplant and that baggage comes back to haunt the recipient with a shorter life and shorter kidney survival. From the conclusion:

…the longer patients wait on dialysis for a transplant the longer patients are exposed to the chronic effects of end-stage renal failure and dialysis. It is well documented that patients on dialysis have alterations in the concentration of a number of substances (e.g., homocysteine, advanced glycosylation end products, and lipoproteins) that may predispose these patients to both cardiovascular and renal allograft vascular damages. In addition, the poor nutrition, chronic in- flammatory state, altered immunologic function, and inade- quate clearance that often accompanies patients with ESRD on dialysis may predispose these patients to poorer toler- ance to the immunosuppressive agents after transplantation.

On our journal club last week we looked at a study by Schold, et al. that analyzed time on dialysis prior to transplant by dividing it into time prior to wait list and time after being listed. They found that all of the risk from prolonged dialysis comes from the time prior to being placed on the transplant wait list:

The data was more dramatic for graft loss than for mortality. The intersting part of this is trying to explain this discrepancy.  Why would time on dialysis prior to wait listing be any different that time on dialysis after wait listing? There is no biological difference so the authors conclude that the difference must be in a subtle, previously unmeasured difference in co-morbidity or access to care. The authors go on to pre-suppose that efforts to reduce patient exposure to dialysis may not yield the benefits one might expect if these other factors are not also corrected.

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Rapamycin came from Easter Island

English: A plaque reminding of the discovery of rapamycin (sirolimus) on Rapa Nui (Easter Island), near Rano Kau. The plaque is written in Brazilian Portuguese, and reads: In this location were obtained, in January 1965, soil samples that allowed for the obtainment of rapamycin, a substance that inaugurated a new era for organ transplant patients. An homage from the Brazilian investigators, November 2000.