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The Ultimate Gift
A
newsletter from the transplant team
at Rhode Island Hospital
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Living Donor Kidney Transplantations:
A Quiet Revolution
For many years the use of living donor kidneys was limited to
donors from the immediate family, so-called first-degree relatives.
It was considered ethically acceptable to use donors from the immediate
family because of the high likelihood of increased tissue matching
(histocompatibility) which would decrease the tendency for graft
rejection and improve graft survival and longevity. Use of living
donors beyond the immediate family or totally unrelated donors was
not considered ethically justified because the chances for increased
tissue matching were very low. Distant relatives or unrelated donors
were considered potentially no better than randomly selected cadaver
donors. This concept was proven totally wrong by Paul Terasaki and
colleagues in a landmark study in 1995 (Terasaki, P.I. et al High
survival rates of kidney transplants from spousal and living unrelated
donors, New England Journal of Medicine 333, 333-336, 1995). Using
the accumulated kidney transplant data from the United Network for
Organ Sharing (UNOS), these authors studied that relatively small
number of recipients who had received living donor kidneys from
spousal and unrelated donors. They showed that the survival rates
of such kidneys were higher than that of cadaver kidneys despite
the fact that the degree of histocompatibility (mismatching) was
frequently higher in the living unrelated donor group. Three-year
survival rates were 85 % for kidneys from spouses, 81 % for living
unrelated donors (not married to the recipient) versus 82% for parental
donors and only 70% for cadaver donors. The superior survival rate
of grafts from unrelated donors could not be attributed to better
HLA matching, white race, younger donor age or shorter cold ischemia
times. The most likely explanation was that kidneys removed from
living donors sustain much less damage than do cadaver kidneys which
are frequently subjected to varying degrees of hypotensive shock
prior to removal.
The authors appropriately concluded that with the currently effective
methods of immunosuppression living unrelated donors—spouses,
friends, lovers, etc.—are important sources of living donor
kidney grafts because, despite poor HLA matching, the graft survival
rate is similar to that of parental donor kidneys and definitely
superior to cadaver donor kidneys. This high survival rate was attributed
to the fact that the kidneys were uniformly more healthy from a
physiologic point of view.
Terasaki's publication served to catalyze a trend which was beginning
even prior to his landmark work.
Recent statistics from UNOS show that,
- Over the past ten years living donor kidney transplants have
more than doubled (from 2,124 donors in 1990 to 4,712 in 2005).
- Among living donors, the percentage of sibling donors has fallen
dramatically (52% in 1990, 35% in 2005). Parental donors have
also decreased (18% in 2005 from 29% in 1990) Living donors increased
primarily among offspring, other relatives and especially unrelated
donors, accounting for 45% of living donors in 2005. Most dramatically,
unrelated donors quadrupled between 1990 and 2005, from 5% to
20%.
- Perhaps the most dramatic statistic relative to living donor
kidney transplants is that recipients of living donor kidneys
accounted for 36% of all recipients (cadaveric and living) in
2005, up from 22 percent of recipients in 1990 and 33% in 1997.
In the Rhode Island Kidney Transplant Program, 51% of kidney transplants
were from living donors in 2005—a statistic that reflects our
diligent efforts to find living donors for our patients.
- In addition to the immediate improvement of short-term graft
survival in recipients of living versus cadaver kidney grafts,
it must be kept in mind that long-term graft survival is distinctly
superior with living donor kidney grafts. The transplant half-life,
the number of years which pass before 50% of the kidneys are rejected
is currently 10.4 years for cadaver grafts but 16.7 years for
living kidney grafts (Ceeka, JM and Terasaki PL, Clinical Transplants
1998, UCLA Publishing 1998). Some analyses project the transplant
half-life to be over twenty-five years for living donor kidney
transplants using newer forms of immunosuppression.
The realization that living donor kidney grafts irrespective of
the degree of HLA histocompatibility provide superior short and
long-term survival over cadaver grafts emphasizes that every effort
must be made to identify all potential living donors for the end-stage
renal disease patient. The only absolute immunological requirement(s)
for inclusion as a potential living donor is ABO compatibility and
a negative pre-transplant recipient-donor crossmatch (i.e. absence
of anti-donor HLA antibody in the recipient). Obviously if more
than one potential donor is available—and if all other considerations
are equal-the donor with the least HLA mismatch is still preferable
over cadaver donors. But as emphasized by Terasaki's studies, totally
mismatched living donors are acceptable and desirable. Identification
of a suitable living donor can insure the end-stage renal disease
patient many years of high quality, dialysis-free life.
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