by George Taniwaki

The American Transplant Congress was held in Seattle (where I live) in May 2013. Unfortunately, I was unable to obtain a press pass. However, I was able to review the abstracts of the papers published in the Amer J Transpl May 2013 (subscription required). Concurrent session 10 was entitled Obesity and Other Comorbid Conditions in Living Kidney Donors. There were six papers in this session. The results were not surprising and the most of them were not positive.

The biggest issue is that the number of Americans who are obese is rising. Obesity is correlated with high blood pressure, coronary heart disease, and Type 2 diabetes. These conditions are all correlated with kidney disease, which has increased dramatically in the U.S. Thus obesity is one of the factors driving an increase in the need for kidney transplants.

Further, overweight and obese patients are more likely to experience complications from surgery. This makes them less likely to become candidates for transplant therapy. On the donor side, obesity makes it harder to be accepted as a donor. With rising obesity in the population, this trend may be exacerbating the shortage of kidney donors.

More donors are less-than-healthy

The first paper in the session (Abstract #69) was entitled “Marked Increase in Pre-Existing Morbidity among Living Kidney Donors in the United States.” The study led by J. Schold at the Cleveland Clinic looked at national data from 1998 to 2010. They discovered a significant rise in comorbidities (presence of diseases unrelated to being a kidney donor) over time. That is, hospitals are accepting more donors who are less healthy than in the past. By 2010 the overall proportion of comorbid conditions was still under 5%, but the trend is troubling.

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Figure 1. Obesity, depression, chronic pulmonary disorders, hypertension, and hypothyroidism are all increasing among people accepted as living kidney donors

Rising obesity makes finding donors harder

The next paper (Abstract# 70) is entitled “Obesity Is a Major Barrier to Increasing Living Kidney Donation in the United States.” The study was led by  Zoe Stewart at University of Iowa Hospitals and Clinics, She examined two years of data from a Midwest hospital (presumably the one she works at) to determine the demographic characteristics (age, gender, ethnicity, biological relationship, obesity measured as BMI, marital status, state residency, and education level).

There were a total of 450 potential donors during the two years. The first table shows the actual outcomes of potential donors. Notice that only 12% of potential donors end up actually donating. This reinforces the message that patients should not stop looking for a donor after finding the first one. They must continue the search until the transplant is complete.

Potential living kidney donor outcome Number Percent of total
Accepted and completed transplant   52   12%
Not transplanted
   Recipient ineligible or received transplant 121    27%
   Withdrew after evaluation started   84   19%
   Not accepted* 193   43%
Total 450 100%

*Major reasons for denial included: hypertension (10.2%), BMI>35 (9.6%), renal disease (6.2%), and cardiovascular disease (2.9%).

The second table shows the demographic differences between potential donors that were accepted and transplanted and those who were not. Statistically significant differences are highlighted.

Unfortunately, the table doesn’t shows the demographic differences for each type of potential donor that was not transplanted. Specifically, donors that were not accepted for medical reasons would be more likely to have high BMI than those who didn’t donate because the recipient received a transplant from another donor.

A few differences stick out.

  1. White, non-Hispanics are accepted at about twice the rate of African-Americans or Hispanics.
  2. Unrelated potential donors are less likely to be accepted than related donors. I speculate this may be because they are more likely to withdraw than related donors.
  3. Nondirected donors are accepted at three times the rate of directed donors. This is probably a self-selection bias. Typically, only very healthy individuals would consider becoming a nondirected donor.
  4. Out of state potential donors are more likely to be accepted than local ones. I speculate that this is because someone willing to travel to donate is less likely to withdraw.
  5. Potential donors with higher education are more likely to be accepted. Perhaps this is because people with higher levels of education are less likely to withdraw. But I speculate that education is a proxy variable for two other factors. Education level is correlated with ethnicity (whites more likely to have gone to college) and with income (which is correlated with better ability to take time off from work and with greater access to healthcare insurance coverage).
Demographics of living donor candidate Accepted and transplanted (N=52) Not accepted (N=398) Acceptance rate
Age 39.9 yr 42.2 yr   –
Gender
   Male 40% 34% 13%
   Female 60% 66% 11%
Ethnicity
   White 94% 88% 12%
   African-American   4%   8%   6%
   Asian    –   0.5%   –
   Hispanic, any race    2%   3.5%   7%
Mean BMI 25.9 28.9   –
Relationship
   Related 58% 54.5% 12%
   Unrelated 37% 44% 10%
   Nondirected   6%   1.5% 34%
Marital status
   Married 61.5% 59% 12%
   Single 27% 27% 11%
   Divorced 11.5% 12% 11%
   Widowed   2%   –
State residency
   Resident >63% 72% 10%
   Nonresident 37% 28% 15%
Education
   < High school   2%   3%   8%
   High school 27% 30% 10%
   Some college 23% 27% 10%
   Associates degree   8% 10% 9%
   Bachelors degree 26% 22% 14%
   Graduate degree 12%   7% 18%

Cigarette smoking in donors leads to lower graft survival

A paper (Abstract #71) by S. Waits et al. at the University of Michigan entitled “Cigarette Smoking in Living Kidney Donors and Graft Survival” shows that people who smoke hurt not only their own health but also reduce the graft survival of kidneys they donate. A study of 635 living kidney transplants showed that 26% of donors smoked within the year prior to transplant. A Kaplan-Meier survival analysis estimated that 5 years and 10 years after transplant, patients who received a kidney from a smoker had a 10% higher chance of losing the graft than those who received a kidney from a nonsmoker.

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Figure 2. Patients who receive a transplant from a donor who smokes were 10% more likely to lose the graft

It is better to get an older living donor now rather than wait for standard criteria deceased donor

One of the most difficult decisions that kidney patients and their medical staff must make is whether to accept a transplant from an older donor or wait for a younger deceased donor. An analysis (Abstract 72) by R. Sapir-Pichhadze and colleagues at the University of Toronto shows that a 40-year-old dialysis patient receiving a live donor transplant from an 60 year-old living donor can achieve to the same quality adjusted life expectancy (QALE) as waiting for a 30 year-old deceased donor kidney.

The study was conducted using a probabilistic Markov model.

My only comment here is that in theory it would be possible to use a kidney exchange to better match the age of patients and donors. Since there is such a shortage of donor organs, having the older living donor participate in the exchange would increase the total number of transplants performed.

Potential living donors with prediabetic condition are acceptable

Some good news for patients whose potential donor is prediabetic. A study (Abstract 73) by S. Shandran and colleagues at Univ. California San Francisco compared 45 prediabetic donors with 45 normal controls from 1996 to 2007 and found little difference in outcomes. The controls were matched for similar medical characteristics including family history of diabetes.

The mean age of both group of donors at the time of donation was about 47 years. At 30 days after donation both groups had a mean eGFR of about 60 ml/min. The main difference was the mean fasting plasma glucose was 109 mg/dl for the prediabetic group compared to 87 for the controls.

The follow-up study occurred a mean of 10 years after donation. For the original prediabetic group, the mean fasting plasma glucose was now 104.7 mg/dl with only 3 donors (7%) over 125 mg/dl. Only 7 (16%) of the prediabetic donors developed diabetes compared to 1 (2%) of the controls. Their eGFR was 70.7 compared to 67.3 for the controls.

Small donors lead to worse kidney function

The final paper of the session (Abstract 74) looks at the effect of small donor size and donor-to-recipient size mismatch on recipient kidney function. We know that many surgeons reject small donors because they are afraid that poor outcomes will result, but there is very little data on it.

This study was conducted by H. Khamash and colleagues at the Mayo Clinic in Phoenix, Arizona. It was a retrospective study of 579 donor recipient pairs from July 2003 to November 2010, excluding repeat or multiorgan transplants, those with positive crossmatch or presence of DSA, or those with early graft loss or death with functioning graft.

Using an unspecified multivariate analysis, the study found that smaller donor size (defines as body surface area <1.7m^2) older donors (defined as donor more than 10 years older than recipient), and lower donor eGFR (defined as under 40 ml/min) independently associated with lower GFR at one year post living donor kidney transplant. Thus, donor size should continue to be considered a factor when assessing the desirability of a donor for transplant.

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